A Study of LY3374849 in Healthy Participants

Study Overview
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Brief Summary
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The aim of this trial is to evaluate the safety and tolerability of the study drug known as LY3374849, when given as an injection to healthy participants. The study will also investigate how quickly the body absorbs and gets rid of LY3374849 and how it affects the levels of blood sugar in comparison to insulin degludec, after a single dose is given by injection under the skin and directly into a vein. Participation in this study includes screening, which is required within 28 days before start of study and a follow up at least 28 days after receiving the last dose of study drug. This study has 3 parts: Participants in Part A will complete 1 study period (approximately 1 week). Participants in Part B will complete 3 study periods (approximately 3 weeks). Participants in Part C will complete 2 study periods (approximately 2 weeks).

Detailed Description
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Parts B and C added per protocol amendment, approved in April 2019.

Official Title
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A Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetic, and Glucodynamic Effects of LY3374849 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: LY3374849 - SC
* Drug: Insulin Degludec - SC
* Drug: LY3374849 - IV
* Drug: Insulin Degludec - IV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or a female who cannot become pregnant Have a body mass index (BMI) of at least 18 kilogram per square meter (kg/m²) Have normal blood pressure, pulse rate, electrocardiogram (ECG), blood and urine laboratory test results that are acceptable for the study Have veins suitable for easy blood collection and glucose solution infusion Exclusion Criteria: Are currently participating in or completed a clinical trial within the last 30 days or any other type of medical research judged to be incompatible with this study Had donated or had blood loss of more than 450 milliliters (mL) within the last 3 months Have a regular alcohol intake greater than 21 units/week (male), or 14 units/week (female) Smoke more than 10 cigarettes per day Are infected with hepatitis B or human immunodeficiency virus (HIV) Have a history of allergies or reactions to more than one drug, or significant severe drug allergy Are taking illegal drugs

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 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: Parallel Assignment
Interventional Model Description: Parts B and C are crossover design.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3374849 - SC (Part A)<br>Single subcutaneous (SC) dose of LY3374849 | Drug: LY3374849 - SC<br>* Administered SC<br>|
| Experimental: Insulin Degludec - SC (Part A)<br>Single SC dose of insulin degludec | Drug: Insulin Degludec - SC<br>* Administered SC<br>|
| Experimental: LY3374849 - SC (Part B)<br>Single dose of LY3374849 administered SC in up to three of three study periods | Drug: LY3374849 - SC<br>* Administered SC<br>|
| Experimental: LY3374849 - IV (Part B)<br>Single dose of LY3374849 administered intravenously (IV) in up to one of three study periods | Drug: LY3374849 - IV<br>* Administered IV<br>|
| Experimental: LY3374849 - IV (Part C)<br>Single IV dose of LY3374849 in one of two study periods | Drug: LY3374849 - IV<br>* Administered IV<br>|
| Experimental: Insulin Degludec - IV (Part C)<br>Single IV dose of insulin degludec in one of two study periods | Drug: Insulin Degludec - IV<br>* Administered IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module | Baseline up to study completion (estimated at 11 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucodynamics: Total Amount of Glucose Infused (Gtot) | Glucodynamics: Gtot | Baseline up to 36 hours post-dose for each study arm | 
| Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3374849 | Pharmacokinetics: AUC of LY3374849 | Baseline at predose through 6 days post-dose for each study arm |