A Study of LY900014 Formulations in Healthy Participants

Study Overview
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Brief Summary
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This study evaluated four test formulations of a glucose lowering drug (LY900014) administered by injection under the skin of the abdomen. The study was conducted in healthy people to investigate how the human body handles LY900014 and the effect of LY900014 on blood sugar levels. Side effects and tolerability were documented. The study was to be conducted in two parts (Part A and Part B) to achieve its objectives. Each part of the study was to last for about 11 to 12 weeks, including screening and follow up. Screening was required within 28 days prior to entering into either study Part A or Part B. Part B was not executed because no suitable formulation was identified.

Official Title
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Safety, Tolerability, Pharmacokinetics and Glucodynamics of Multiple Insulin Lispro (LY900014) Formulations

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Biological: LY900014
* Biological: Insulin Lispro


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overtly healthy male or a female (not pregnant and agreeable to take birth control measures until one month after study completion) Have a body mass index (BMI) of 18.5 to 30 kilogram per square meter (kg/m^2), inclusive, at screening Have normal blood pressure, pulse rate, electrocardiogram (ECG), blood and urine laboratory test results that are acceptable for the study Are nonsmokers, have not smoked for at least 2 months prior to entering the study, and agree not to smoke (cigars, cigarettes, or pipes) or use smokeless tobacco for the duration of the study Exclusion Criteria: Are currently participating in or completed a clinical trial within the last 30 days from a clinical trial or any other type of medical research judged to be incompatible with this study Have previously participated or withdrawn from this study Have or used to have health problems or laboratory test results or ECG readings that, in the opinion of the doctor, could make it unsafe to participate, or could interfere with understanding the results of the study

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: Part A: LY900014 Test A<br>Test Formulation A. Single dose of LY900014 administered subcutaneously (SC) in one of five periods. | Biological: LY900014<br>* Administered SC<br>* Other names: Ultra-Rapid Lispro;|
| Experimental: Part A:Insulin Lispro<br>Reference formulation. 15 U insulin lispro administered SC in one of five periods. | Biological: Insulin Lispro<br>* Administered SC<br>* Other names: LY275585;|
| Experimental: Part A: LY900014 Test B<br>Test Formulation B. Single dose LY900014 administered subcutaneously (SC) in one of five periods. | Biological: LY900014<br>* Administered SC<br>* Other names: Ultra-Rapid Lispro;|
| Experimental: Part A: LY900014 Test C<br>Test Formulation C. Single dose LY900014administered subcutaneously (SC) in one of five periods. | Biological: LY900014<br>* Administered SC<br>* Other names: Ultra-Rapid Lispro;|
| Experimental: Part A: LY900014 Test D<br>Test Formulation D. Single dose LY900014administered subcutaneously (SC) in one of five periods. | Biological: LY900014<br>* Administered SC<br>* Other names: Ultra-Rapid Lispro;|
| Experimental: Part B: LY900014<br>Test formulation selected from Part A. Single dose of LY900014 administered SC in one of four periods. | Biological: LY900014<br>* Administered SC<br>* Other names: Ultra-Rapid Lispro;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Pharmacokinetics (PK ): Area Under the Concentration Curve From Zero to the Last Recorded Time Post Dose (AUC0-tlast) |  | 30 minutes predose, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Visual Analog Scale (VAS) Score for Injection Site Pain | The Visual Analog Scale (VAS) assessed injection site pain on a scale of 0-100 millimeter (mm) range (0 = no pain and 100 worst imaginable pain). | Predose, 1, 20, 60 minutes postdose and at the end of the clamp procedure | 
| Part A: Total Amount of Glucose Infused (Gtot) Over the Duration of Clamp | 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. | Every 10 minutes for 30 minutes predose, every 2.5 minutes for 30 minutes, then every 5 minutes for 120 minutes, then every 10 minutes for 300 minutes postdose | 
| Part B: Total Amount of Glucose Infused (Gtot) Over the Duration of the Clamp - Interparticipant Variability | 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. | Every 10 minutes for 30 minutes predose, every 2.5 minutes for 30 minutes, then every 5 minutes for 120 minutes, then every 10 minutes for 300 minutes, then every 20 minutes from 300 to 480 minutes postdose | 
| Part B: Pharmacokinetics (PK): Area Under the Concentration Curve From Zero to the Last Recorded Time Post Dose (AUC0-tlast) - Interparticipant Variability |  | Predose, 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 70, 90, 120, 150, 180, 240, and 300 minutes postdose |