A Study to Compare LY2963016 and US-approved Lantus® After Single Dose Administration to Healthy Participants

Study Overview
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Brief Summary
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The purpose of this study is to compare the pharmacokinetics and pharmacodynamics of LY2963016 and US-approved Lantus®. The study involves four single injections; two doses of LY2963016 and two doses of US-approved Lantus®. The study will have 4 periods. In each period, a single injection will be administered before undergoing a euglycemic clamp that lasts for 24 hours. There will be at least a 7 day washout between each period. Side effects will be documented. Study participation is expected to last up to 14 weeks.

Official Title
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Comparative Pharmacokinetics and Pharmacodynamics of LY2963016 and US-Approved Lantus® After Single-Dose Subcutaneous Administration to Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: LY2963016
* Drug: US Approved Lantus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are overtly healthy males or females Have body mass index between 18.5 and 29.9 kilograms per meter square (kg/m^2) Are nonsmokers and have not smoked for at least 2 months prior to entering the study Have normal blood pressure and pulse rates at screening Have electrocardiograms (ECGs) at screening considered as within normal limits Have clinical laboratory test results within normal reference ranges Exclusion Criteria: Are currently enrolled in or discontinued within the last 30 days from a clinical study involving an investigational drug or device or are concurrently enrolled in any other type of medical research 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 Show evidence of significant active neuropsychiatric disease, including taking prescription medication for such diseases Show evidence of current use of known drugs of abuse or a history of use within the past year Have a history of first-degree relatives known to have diabetes mellitus Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies at screening Have positive hepatitis B surface antigen at screening Intend to use over-the-counter or prescription medication within 7 or 14 days, respectively, prior to dosing (apart from vitamin/mineral supplements, occasional paracetamol, thyroid replacement medication, or birth control methods) Have donated or had a blood loss of 450 milliliters (mL) within 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 24 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: LY2963016<br>Single 0.5 units per kilogram (U/kg) dose of LY2963016 administered subcutaneously, twice during the study | Drug: LY2963016<br>* Administered subcutaneously<br>|
| Experimental: US-approved Lantus<br>Single 0.5 U/kg dose of US-approved Lantus administered subcutaneously, twice during the study | Drug: US Approved Lantus<br>* Administered subcutaneously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Time Curve (AUC) of LY2963016 and US-Approved Lantus | The AUC from time 0 to 24 hours (AUC0-24) of LY2963016 and US-Approved Lantus was measured. | 30 minutes predose up to 24 hours postdose in all treatment periods | 
| Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) of LY2963016 and US-Approved Lantus |  | 30 minutes predose up to 24 hours postdose in all treatment periods | 

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 target blood glucose level 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 LY2963016 or US-approved Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight. | 30 minutes predose up to 24 hours postdose in all treatment periods | 
| Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp Procedure | Gtot was the total glucose infusion over the clamp duration and was used to measure the study drug action over time as measured by the euglycaemic clamp procedure. During the euglycaemic clamp procedure, blood glucose concentrations were held constant after the administration of LY2963016 or US-approved Lantus by adjusting the exogenous glucose infusion rate. Data presented were adjusted by the body weight. | 30 minutes predose up to 24 hours postdose in all treatment periods | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Volunteers