A Study of LY2605541 Versus Insulin Glargine on Blood Sugar

Study Overview
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Brief Summary
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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.

Official Title
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Comparison of the Effects of LY2605541 and Insulin Glargine on Endogenous Glucose Output and Peripheral Glucose Disposal in Healthy Subjects and Patients With Type 1 Diabetes Mellitus

Conditions
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Healthy Volunteers, Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: LY2605541
* Other: Insulin glargine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A, Cohort A; LY2605541<br>Healthy participants received 5.1 milliunits/minute (mU/min) in Period 1, 10.2 mU/min in Period 2, and 15.3 mU/min in Period 3, administered intravenously (IV) over 8 hours. All periods were separated by a minimum 6-day washout period | Drug: LY2605541<br>* LY2605541 is a solution. The concentration of LY2605541 is 100 units/milliliter (U/mL).<br>|
| Active Comparator: Part A, Cohort A; Insulin Glargine<br>Healthy participants received insulin glargine (30 milliunits/meter squared/minute [mU/m^2/min]) administered IV over 8 hours in Period 4. All periods were separated by a minimum 6-day washout period | Other: Insulin glargine<br>* Insulin glargine is a 100 U/mL solution in 10 milliliter (mL) glass vial.<br>|
| Experimental: Part A, Cohort B; LY2605541<br>Healthy participants received 15.3 mU/min in Period 1, 37.0 mU/min in Period 2, and 74.1 mU/min in Period 3, administered IV over 8 hours. All periods were separated by a minimum 6-day washout period. | Drug: LY2605541<br>* LY2605541 is a solution. The concentration of LY2605541 is 100 units/milliliter (U/mL).<br>|
| Active Comparator: Part A, Cohort B; Insulin Glargine<br>Healthy participants received insulin glargine (60 mU/m^2/min) administered IV over 8 hours in Period 4. All periods were separated by a minimum 6-day washout period. | Other: Insulin glargine<br>* Insulin glargine is a 100 U/mL solution in 10 milliliter (mL) glass vial.<br>|
| Experimental: Part B; LY2605541<br>Participants with T1DM received 15.3 mU/min in 1 of 4 study periods, administered IV up to 8 hours and received 74.1 mU/min in 1 of 4 Periods, administered IV up to 10 hours. Each dose was separated by a minimum 6-day washout period. | Drug: LY2605541<br>* LY2605541 is a solution. The concentration of LY2605541 is 100 units/milliliter (U/mL).<br>|
| Active Comparator: Part B; Insulin Glargine<br>Participants with T1DM received 1 insulin glargine dose per study period (10 and 20 mU/m^2/min) administered IV over 8 hours in 2 of 4 study periods. Each dose was separated by a minimum 6-day washout period. | Other: Insulin glargine<br>* Insulin glargine is a 100 U/mL solution in 10 milliliter (mL) glass vial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, up to 10 hours (duration of the euglycemic glucose clamp) | 
| 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. | Baseline, up to 10 hours (duration of the euglycemic glucose clamp) | 
| 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. | Baseline, up to 10 hours (duration of the euglycemic glucose clamp) |