Diabetes Mellitus, Type 1
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, and to measure the quantity of LY2605541 in fat tissue. The study has two parts. It involves intravenous (IV) infusion of the investigational drug and a procedure to measure concentrations in the fat tissue. Both parts of the study will be conducted in participants with type 1 diabetes mellitus (T1DM). Part A and B of the study might take up to 7 weeks to complete.
Interventions
Administered IV
DRUGHuman Insulin
Administered IV
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Have a diagnosis of Type 1 Diabetes Mellitus (T1DM) based on medical history for at least 1 year prior to enrollment * Have a c-peptide value ≤0.3 nanomoles per liter (nmol/L) at screening * Have a serum creatinine value within normal limits at screening * Have a haemoglobin A1c (HbA1c) value ≤75 millimoles per mole (mmol/mol) (9.0%) at screening * Have a body mass index (BMI) of 20.0-30.0 kilograms per meter squared (kg/m\^2), inclusive, at screening
Exclusion criteria
* Have known or suspected allergies or hypersensitivities to LY2605541, human insulin, sinistrin, related compounds or any components of the formulations * Are women who are pregnant or lactating * Have an abnormal blood pressure for the population as determined by the investigator * Have renal insufficiency or major renal disorders * Have proliferative retinopathy or maculopathy * Have lipodystrophy * Have any wound healing disorder or are prone to keloid or hypertrophic scar formation * Have results of screening prothrombin time (PT) and international normalized ratio (INR) tests that are significantly prolonged * Have a fasting triglycerides value \> 4.52 millimoles per liter (mmol/L) (400 milligrams/deciliter (mg/dL)) * Are receiving chronic systemic or inhaled glucocorticoid or have received such therapy within the 4 weeks before dosing * Have a total daily insulin dose greater than 1.2 units per kilogram (U/kg) * 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 * Regular use or intended use of non-selective beta blockers * Regular use or intended use of monoamine oxidase (MAO) inhibitors * Are currently participating in a weight loss program or plan to do so during the course of the study * Are unwilling to avoid excessive sun exposure, steam baths, saunas, and swimming during the study. Sun cream should be used during sun bathing for the 6-month period following the study * Are unwilling to avoid extensive consumption of food containing inulin during the study and in the 48-hour period leading up to the clamp
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Pharmacokinetics: Steady-State Concentrations in Adipose Tissue Interstitial Fluid (ISF) | 16, 20, 24, and 28 hours postdose | — |
| Part B: Pharmacokinetics: ISF-to-Serum Concentrations | 16, 20, 24, and 28 hours postdose | Absolute concentration of ISF of insulin peglispro and human insulin. |
Countries
Austria
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Part A Low/High Insulin Peglispro Participants received 4.00 U priming dose and 1.84 U/h constant IV infusion or 8.00 U priming dose and 4.50 U/h constant IV infusionconstant IV infusion of insulin peglispro for 36 hours with up to 2 weeks between doses. | 4 |
| Part A Intermediate Insulin Peglispro Participants received 4.00 U priming dose and 1.84 U/h constant IV infusion or 6.00 U priming dose and 2.76U/h constant IV infusion constant IV infusion of insulin peglispro for 36 hours with up to 2 weeks between doses. | 8 |
| Part B Participants first received a priming dose of 8.00 U followed by 2.76 U/h constant intravenous (IV) infusion of LY2605541 for 36 hours or 6 pmol/kg/min constant infusion of human insulin with up to 2 weeks between doses. | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Part B | Adverse Event | 0 | 0 | 0 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Part A Low/High Insulin Peglispro | Part A Intermediate Insulin Peglispro | Part B | Total |
|---|---|---|---|---|
| Age, Continuous | 40.0 years STANDARD_DEVIATION 13.2 | 39.0 years STANDARD_DEVIATION 7.9 | 40.9 years STANDARD_DEVIATION 13.6 | 40.1 years STANDARD_DEVIATION 11.4 |
| BMI | 27.57 kilograms per meter squared (kg/m²) STANDARD_DEVIATION 2.09 | 25.98 kilograms per meter squared (kg/m²) STANDARD_DEVIATION 1.87 | 26.73 kilograms per meter squared (kg/m²) STANDARD_DEVIATION 1.28 | 26.62 kilograms per meter squared (kg/m²) STANDARD_DEVIATION 1.65 |
| Body Weight | 83.93 kilograms (kg) STANDARD_DEVIATION 12.63 | 83.80 kilograms (kg) STANDARD_DEVIATION 8.79 | 83.56 kilograms (kg) STANDARD_DEVIATION 8.6 | 83.70 kilograms (kg) STANDARD_DEVIATION 8.93 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 8 Participants | 12 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| HbA1c | 7.20 percentage of Glycated hemoglobin STANDARD_DEVIATION 0.88 | 7.51 percentage of Glycated hemoglobin STANDARD_DEVIATION 0.9 | 7.53 percentage of Glycated hemoglobin STANDARD_DEVIATION 0.54 | 7.47 percentage of Glycated hemoglobin STANDARD_DEVIATION 0.71 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 8 Participants | 12 Participants | 24 Participants |
| Region of Enrollment Austria | 4 Participants | 8 Participants | 12 Participants | 24 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 3 Participants | 8 Participants | 10 Participants | 21 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 3 / 8 | 1 / 8 | 0 / 4 | 4 / 12 | 2 / 11 |
| serious Total, serious adverse events | 0 / 4 | 0 / 8 | 0 / 8 | 0 / 4 | 0 / 12 | 0 / 11 |
Outcome results
Primary
Part B: Pharmacokinetics: ISF-to-Serum Concentrations
Absolute concentration of ISF of insulin peglispro and human insulin.
Time frame: 16, 20, 24, and 28 hours postdose
Population: All participants who received at least 1 dose of study drug in Part B and had evaluable pharmacokinetic data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Insulin Peglispro | Part B: Pharmacokinetics: ISF-to-Serum Concentrations | 1428.4 picomol per liter (pmol/L) |
| Human Insulin | Part B: Pharmacokinetics: ISF-to-Serum Concentrations | 137.9 picomol per liter (pmol/L) |
Primary
Part B: Pharmacokinetics: Steady-State Concentrations in Adipose Tissue Interstitial Fluid (ISF)
Time frame: 16, 20, 24, and 28 hours postdose
Population: All participants who received at least 1 dose of study drug in Part B and had evaluable pharmacokinetic data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Insulin Peglispro | Part B: Pharmacokinetics: Steady-State Concentrations in Adipose Tissue Interstitial Fluid (ISF) | 11200 picomol per liter (pmol/L) | Geometric Coefficient of Variation 23 |
| Human Insulin | Part B: Pharmacokinetics: Steady-State Concentrations in Adipose Tissue Interstitial Fluid (ISF) | 425 picomol per liter (pmol/L) | Geometric Coefficient of Variation 15 |