A Study to Compare LY2963016 to Lantus After a Single Dose to Participants With Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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The study involves a single injection of LY2963016 and a single injection of Lantus, on 2 separate occasions in participants with type I diabetes. Following each dose, participants will undergo a glucose clamp which lasts for 42 hours each time. There will be at least 7 days between the two periods, during which time there will be no study treatment, but participants will resume their regular therapy. The duration of this study can be up to 9.5 weeks. The purposes of this study are to understand how the blood sugar lowering effect of LY2963016 compares to that of Lantus, and to determine how LY2963016 and Lantus are metabolized by participants with type I diabetes.

Official Title
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Pharmacodynamics of LY2963016 Compared to LANTUS® in Subjects With Type 1 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: LY2963016
* Drug: Lantus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: have type 1 diabetes mellitus (T1DM) based on the disease diagnostic criteria have had a duration of diabetes ≥1 year have hemoglobin A1c ≤10.0% have fasting C-peptide ≤0.3 nanomoles per liter (nmol/L) have a body mass index ≤29 kilograms per square meter (kg/m²) have venous access sufficient to allow blood sampling and cannulation for clamp procedures Exclusion Criteria: are currently enrolled in, have completed, or discontinued within the last 30 days from, a clinical trial involving an investigational drug or device or off-label use of a drug or device have a total insulin requirement >1.2 units per kilogram per day (U/kg/day) have a history of proliferative retinopathy have known allergies to insulin glargine, insulin lispro, heparin, or related compounds have an electrocardiogram (ECG) reading considered outside the normal limits have an abnormal blood pressure have abnormal clinical laboratory tests have a history or presence of/significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs history of deep leg vein thrombosis or a frequent appearance of deep leg vein thrombosis in first-degree relatives show evidence of significant active neuropsychiatric disease regular use of known drugs of abuse and/or show positive findings on drug screening show evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies show evidence of hepatitis C and/or positive hepatitis C antibody show evidence of hepatitis B and/or positive hepatitis B surface antigen are women with a positive pregnancy test or women who are lactating have an average weekly alcohol intake that exceeds 21 units per week (males) or 14 units per week (females) had more than 1 episode of severe hypoglycemia within 6 months prior to study undergoing therapy for a malignancy other than basal cell or squamous cell skin cancer had a blood transfusion or severe blood loss within 3 months; made a blood donation within 30 days prior to study entry; or have known hemoglobinopathy, haemolytic anemia, or sickle cell anemia are receiving systemic glucocorticoid therapy have irregular sleep/wake cycle (for example, participants who sleep during the day and work during the night) show a history of adverse reactions to heparin, including heparin-induced thrombocytopenia smoke more than 10 cigarettes (or equivalent other tobacco products) per day

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY2963016<br>A single 0.3 units per kilogram (U/kg) dose of LY2963016 will be administered subcutaneously followed by a minimum washout period of 7 days. | Drug: LY2963016<br>* Single 0.3 U/kg dose administered subcutaneously<br>|
| Active Comparator: Lantus<br>A single 0.3 U/kg dose of Lantus will be administered subcutaneously followed by a minimum washout period of 7 days. | Drug: Lantus<br>* Single 0.3 U/kg dose administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics: Duration of Action of LY2963016 and Lantus | Duration of action is defined as the period of time elapsed between dose administration and the time at which the participant's blood glucose is consistently >150 milligrams/deciliter (mg/dL) without any glucose infusion. Participants whose blood glucose did not rise to 150 mg/dL were censored 42 hours postdose. | Periods 1 and 2: Baseline up to 42 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Glucose Infusion Rate (Rmax) | Rmax is the maximum infusion rate of glucose administered intravenously needed to maintain a target blood glucose level of 100 milligrams/deciliter (mg/dL) [5.6 millimoles/Liter (mmol/L)] and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations are held constant after the administration of study drug by adjusting the exogenous glucose infusion rate. Data presented are the maximum infusion rates, adjusted by body weight. | Periods 1 and 2: Baseline up to 42 hours postdose | 
| Total Glucose Infused (Gtot) | Gtot is the total glucose infusion over the clamp duration and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations are held constant after the administration of study drug by adjusting the exogenous glucose infusion rate. Data presented are the total glucose infused, adjusted by body weight. | Periods 1 and 2: Baseline up to 42 hours postdose | 
| Time of Maximum Glucose Infusion Rate (tRmax) | tRmax is the time to reach maximum glucose infusion rate and is used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations are held constant after the administration of study drug by adjusting the exogenous glucose infusion rate. | Periods 1 and 2: Baseline up to 42 hours postdose | 
| Pharmacokinetics: Maximum Concentration (Cmax) of LY2963016 and Lantus | Cmax was not analyzed because of insufficient data due to concentrations being below the quantifiable lower limit of the assay. | Periods 1 and 2: Baseline up to 42 hours postdose | 
| Pharmacokinetics: Area Under the Concentration-time Curve (AUC) of LY2963016 and Lantus | AUC was not analyzed because of insufficient data due to concentrations being below the quantifiable lower limit of the assay. | Periods 1 and 2: Baseline up to 42 hours postdose |