Diabetes Mellitus, Type 1, Healthy Volunteers
Conditions
Brief summary
LY2605541 is an investigational drug being developed for the treatment of diabetes mellitus. This study is designed to understand how the body handles the investigational drug, what effect this investigational drug has on the body, and how much should be given. This study will also measure how much of the investigational drug gets into the blood stream and how long it takes the body to get rid of it. The study has 2 parts: Part A will be conducted in healthy participants. Part B will be conducted in participants with type 1 diabetes mellitus (T1DM). This study will take approximately 10-14 days spread over 6-20 weeks, not including screening. Screening will be performed within 30 days of the start of the study.
Interventions
DRUGLY2605541
LY2605541 is a solution. The concentration of LY2605541 is 100 units/milliliter (U/mL).
OTHERInsulin glargine
Insulin glargine is a 100 U/mL solution in 10 milliliter (mL) glass vial.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
All Participants * Are healthy males or participants with T1DM * Have a screening body mass index (BMI) of 20.0-29.9 kilograms per square meter (kg/m\^2) Healthy Participants ONLY * Are overtly healthy, as determined by medical history and physical examination * Have a fasting blood glucose \<108 milligrams/deciliter (mg/dL) (6.0 millimoles/liter \[mmol/L\]) at screening Participants with T1DM ONLY * Have a diagnosis of T1DM for at least 1 year based on medical history * Have a screening c-peptide \<0.5 nanograms/milliliter (ng/mL) * Have a hemoglobin A1c (HbA1c) of 6.0 to 9.0% at screening * Have had no episodes of severe hypoglycemia in the past 6 months
Exclusion criteria
All Participants * Have a hemoglobin level \<12.0 grams/deciliter (g/dL) * Are currently a smoker, used tobacco products on a regular basis in the 6 months prior to screening, or are intending to smoke during the study Healthy Participants ONLY • Regular use or intended use of over-the counter or prescription medication within 7 and 14 days, respectively, prior to dosing (apart from vitamin/mineral supplements or occasional use of acetaminophen or ibuprofen). Participants with T1DM ONLY * Regular use or intended use of any over-the-counter or prescription medications or nutritional supplements that affect blood glucose or the body's sensitivity to insulin or that promote weight loss within 14 days prior to dosing * Are receiving chronic (lasting longer than 14 consecutive days) systemic or inhaled glucocorticoid therapy (excluding topical, intra-articular, and intraocular preparations) or have received such therapy within the 4 weeks before dosing * Require a total daily insulin dose exceeding 100 units (U) * Have fasting triglycerides \>400 mg/dL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Glucodynamics: Endogenous Glucose Output | Baseline, up to 10 hours (duration of the euglycemic glucose clamp) | The percent suppression from baseline in endogenous glucose production (EGP) is presented. Percent EGP change from baseline was calculated by (1-\[last 2 hours of EGP/basal EGP\])\*100. The duration of the clamp procedure was 10 hours for the LY2605541 74.1 mU/min dose in Part B. The duration of the clamp procedures performed at the 15.3 mU/min LY2605541 dose and both of the insulin glargine doses was 8 hours. |
| Part B: Glycodynamics: Glucose Disposal | Baseline, up to 10 hours (duration of the euglycemic glucose clamp) | The fold change from baseline in glucose disappearance rate (GDR) is presented. The fold GDR increase from baseline was calculated by last 2 hours of GDR/basal GDR. The duration of the clamp procedure was 10 hours for the LY2605541 74.1 mU/min dose in Part B. The duration of the clamp procedures performed at the 15.3 mU/min LY2605541 dose and both of the insulin glargine doses was 8 hours. |
| Part B: Glycodynamics: Maximum Rate of Glucose Disposal | Baseline, up to 10 hours (duration of the euglycemic glucose clamp) | The maximum rate of glucose disposal (Rdmax) is presented. The duration of the clamp procedure was 10 hours for the LY2605541 74.1 mU/min dose in Part B. The duration of the clamp procedures performed at the 15.3 mU/min LY2605541 dose and both of the insulin glargine doses was 8 hours. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A All participants who received at least 1 dose of study drug in Part A of the study. | 8 |
| Part B All participants who received at least 1 dose of study drug in Part B of the study. | 14 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part B, Period 1 | Physician Decision | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Part A | Part B |
|---|---|---|---|
| Age, Continuous | 31.6 years STANDARD_DEVIATION 9.3 | 26.1 years STANDARD_DEVIATION 1.5 | 34.7 years STANDARD_DEVIATION 10.5 |
| Race/Ethnicity, Customized Asian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 21 Participants | 7 Participants | 14 Participants |
| Region of Enrollment United States | 22 Participants | 8 Participants | 14 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 22 Participants | 8 Participants | 14 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 2 / 4 | 3 / 8 | 2 / 4 | 1 / 4 | 0 / 4 | 1 / 4 | 1 / 14 | 3 / 13 | 2 / 13 | 5 / 13 |
| serious Total, serious adverse events | 0 / 4 | 0 / 4 | 0 / 8 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 4 | 0 / 14 | 0 / 13 | 0 / 13 | 0 / 13 |
Outcome results
Primary
Part B: Glucodynamics: Endogenous Glucose Output
The percent suppression from baseline in endogenous glucose production (EGP) is presented. Percent EGP change from baseline was calculated by (1-\[last 2 hours of EGP/basal EGP\])\*100. The duration of the clamp procedure was 10 hours for the LY2605541 74.1 mU/min dose in Part B. The duration of the clamp procedures performed at the 15.3 mU/min LY2605541 dose and both of the insulin glargine doses was 8 hours.
Time frame: Baseline, up to 10 hours (duration of the euglycemic glucose clamp)
Population: Participants who received at least 1 dose of study drug with evaluable EGP data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 15.3 mU/Min LY2605541 | Part B: Glucodynamics: Endogenous Glucose Output | 64.53 percent of suppression | Standard Deviation 19.35 |
| 74.1 mU/Min LY2605541 | Part B: Glucodynamics: Endogenous Glucose Output | 99.23 percent of suppression | Standard Deviation 1.76 |
| 10 mU/m^2/Min Insulin Glargine | Part B: Glucodynamics: Endogenous Glucose Output | 78.05 percent of suppression | Standard Deviation 17.33 |
| 20 mU/m^2/Min Insulin Glargine | Part B: Glucodynamics: Endogenous Glucose Output | 97.05 percent of suppression | Standard Deviation 6.47 |
Primary
Part B: Glycodynamics: Glucose Disposal
The fold change from baseline in glucose disappearance rate (GDR) is presented. The fold GDR increase from baseline was calculated by last 2 hours of GDR/basal GDR. The duration of the clamp procedure was 10 hours for the LY2605541 74.1 mU/min dose in Part B. The duration of the clamp procedures performed at the 15.3 mU/min LY2605541 dose and both of the insulin glargine doses was 8 hours.
Time frame: Baseline, up to 10 hours (duration of the euglycemic glucose clamp)
Population: Participants who received at least 1 dose of study drug with evaluable GDR data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 15.3 mU/Min LY2605541 | Part B: Glycodynamics: Glucose Disposal | 0.68 fold change | Standard Deviation 0.09 |
| 74.1 mU/Min LY2605541 | Part B: Glycodynamics: Glucose Disposal | 1.42 fold change | Standard Deviation 0.35 |
| 10 mU/m^2/Min Insulin Glargine | Part B: Glycodynamics: Glucose Disposal | 0.98 fold change | Standard Deviation 0.39 |
| 20 mU/m^2/Min Insulin Glargine | Part B: Glycodynamics: Glucose Disposal | 1.85 fold change | Standard Deviation 0.59 |
Primary
Part B: Glycodynamics: Maximum Rate of Glucose Disposal
The maximum rate of glucose disposal (Rdmax) is presented. The duration of the clamp procedure was 10 hours for the LY2605541 74.1 mU/min dose in Part B. The duration of the clamp procedures performed at the 15.3 mU/min LY2605541 dose and both of the insulin glargine doses was 8 hours.
Time frame: Baseline, up to 10 hours (duration of the euglycemic glucose clamp)
Population: Participants who received at least 1 dose of study drug with evaluable Rdmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 15.3 mU/Min LY2605541 | Part B: Glycodynamics: Maximum Rate of Glucose Disposal | 1.80 milligrams/minute/kilograms (mg/min/kg) | Geometric Coefficient of Variation 24 |
| 74.1 mU/Min LY2605541 | Part B: Glycodynamics: Maximum Rate of Glucose Disposal | 2.89 milligrams/minute/kilograms (mg/min/kg) | Geometric Coefficient of Variation 23 |
| 10 mU/m^2/Min Insulin Glargine | Part B: Glycodynamics: Maximum Rate of Glucose Disposal | 2.15 milligrams/minute/kilograms (mg/min/kg) | Geometric Coefficient of Variation 28 |
| 20 mU/m^2/Min Insulin Glargine | Part B: Glycodynamics: Maximum Rate of Glucose Disposal | 3.55 milligrams/minute/kilograms (mg/min/kg) | Geometric Coefficient of Variation 40 |