A Study of LY2963016 in Healthy Participants

Study Overview
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Brief Summary
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This study involves 2 single injections of LY2963016 and 2 single injections of Lantus. There will be at least 6 days between each injection. The study will compare LY2963016 to Lantus at two different doses. This study is approximately 10 weeks long, not including screening. Screening is required within 4 weeks of the start of the study.

Official Title
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Pharmacokinetics and Pharmacodynamics of LY2963016 Compared to Lantus® in Healthy Subjects Following Two Single Subcutaneous Doses

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: LY2963016
* Drug: Lantus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or females Women must be either surgically sterile, post-menopausal, or agree to use a reliable method of birth control during the study Have a body mass index between 18.5 and 29.9 kilograms per meter squared (kg/m²) Are nonsmokers and have not smoked for at least 6 months prior to entering the study Have normal blood pressures and pulse rates at screening, as determined by the investigator Have an electrocardiogram (ECG) at screening considered as within normal limits by the investigator Have clinical laboratory test results within normal reference range for the population Have fasting plasma glucose <110 milligrams per deciliter (mg/dL) (<6.0 micromoles per liter [mmol/L]) at screening Have venous access sufficient to allow for blood sampling, intravenous drug administration, and clamp procedures as per the protocol Have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site Exclusion Criteria: Are persons who have previously completed or withdrawn from this study Are currently enrolled in or have discontinued within the last 30 days from a clinical trial involving an investigational drug or device or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study Have known allergies to insulin, its excipients, or related drugs or have history of relevant allergic reactions of any origin Have 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; of constituting a risk when taking the study medication; or of interfering with the interpretation of data Show evidence of significant active neuropsychiatric disease Show evidence of current use of known drugs of abuse or have a history of use within the past year Have a history of first-degree relatives known to have diabetes mellitus Show evidence of an acute infection with fever or infectious disease at the time of study entry Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies at screening Have positive hepatitis B surface antigens at screening Intend to use over-the-counter medication within 7 days or prescription medication within 14 days prior to dosing (apart from vitamin/mineral supplements, occasional paracetamol, thyroid replacement, or birth control methods) Have donated blood or had a blood loss of 450 milliliters (mL) 3 months prior to study enrollment Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females) or are unwilling to stop alcohol consumption from 48 hours prior to each dosing until discharged from the clinical research unit (CRU)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.3 U/kg LY2963016<br>Single 0.3 units/kilogram (U/kg) subcutaneous dose of LY2963016 | Drug: LY2963016<br>* Administered subcutaneously<br>|
| Experimental: 0.3 U/kg Lantus<br>Single 0.3 U/kg subcutaneous dose of Lantus | Drug: Lantus<br>* Administered subcutaneously<br>|
| Experimental: 0.6 U/kg LY2963016<br>Single 0.6 U/kg subcutaneous dose of LY2963016 | Drug: LY2963016<br>* Administered subcutaneously<br>|
| Experimental: 0.6 U/kg Lantus<br>Single 0.6 U/kg subcutaneous dose of Lantus | Drug: Lantus<br>* Administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Area Under the Serum LY2963016 or Lantus Concentration-Time Curve (AUC) From Zero to Infinity [AUC(0-∞)] | Results for LY2936016 treatment arms provide the AUC(0-∞) data for LY2936016, while the results for Lantus treatment arms provide the AUC(0-∞) for Lantus. | Predose up to 24 hours after administration of study drug | 
| Pharmacokinetics: Maximum Serum LY2963016 or Lantus Concentration (Cmax) |  | Predose up to 24 hours after administration of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Area Under the Serum Concentration-Time Curve From Time Zero to 24 Hours [AUC(0-24)] of LY2963016 or Lantus | Results for LY2936016 treatment arms provide the AUC(0-24) data for LY2936016, while the results for Lantus treatment arms provide the AUC(0-24) for Lantus. | Predose up to 24 hours after administration of study drug | 
| Pharmacokinetics: Area Under the Serum Concentration-Time Curve (AUC) From Time Zero to Last Measured Concentration Value [AUC(0-tlast)] of LY2963016 or Lantus | Results for LY2936016 treatment arms provide the AUC(0-tlast) data for LY2936016, while the results for Lantus treatment arms provide the AUC(0-tlast) for Lantus. | Predose up to 24 hours after administration of study drug | 
| Maximum Glucose Infusion Rate (Rmax) | Rmax 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 LY2963016 or Lantus by adjusting the exogenous glucose infusion rate. | Postdose up to 24 hours after administration of study drug | 
| Total Amount of Glucose Infused (Gtot) | Gtot 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 LY2963016 or Lantus by adjusting the exogenous glucose infusion rate. | Postdose up to 24 hours after administration of study drug |