A Study of LY2605541 (Insulin Peglispro) and Human Insulin Concentrations in Fat Tissue

Lilly

Status and phase: Completed; Phase 1

Conditions: Diabetes Mellitus, Type 1

Treatments: Drug: Human Insulin; Drug: Insulin Peglispro

Study type: Interventional

Funder types: Industry

Identifiers

NCT02109029

14873

I2R-MC-BIDP (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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24 participants in 2 patient groups

Insulin Peglispro (LY2605541)

Experimental group

Description:

Part A Cohort 1: (low dose) priming dose (PD) of 2.00 units (U), 0.92 U/hour (U/h) constant infusion of insulin peglispro Part A Cohort 1: (high dose) PD of 8.00 U, 4.50 U/h constant IV infusion of insulin peglispro Part A Cohort 2: (intermediate dose 1) PD of 4.00 U, 1.84/h constant IV infusion of insulin peglispro Part A Cohort 2: (intermediate dose 2) PD of 6.0 U, 2.76 U/h constant IV infusion of insulin peglispro Part B Insulin Peglispro: PD of 6.00 U, 2.76 constant IV infusion of insulin peglispro and a constant infusion of 6 pico moles per kilogram per minute (pmol/kg/min). IV infusion of sinistrin (250 mg/mL, SOC to achieve a steady state for up to 16 hours).

Treatment:

Drug: Insulin Peglispro

Human Insulin

Active Comparator group

Description:

Constant IV infusion ( 6 pico moles per kilogram perminute \[pmol/kg/min\]) of human insulin for up to 36 hours. IV infusion of sinistrin (250 mg/mL, SOC to achieve a steady state for up to 16 hours).

Treatment:

Drug: Human Insulin