A Study of LY3143753 and LY3185643 in Healthy Participants

Study Overview
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Brief Summary
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The study involves a single dose of LY3143753 or LY3185643, given as an injection into the abdomen. The study will evaluate the effects of the LY3143753 or LY3185643 on your body. The study is approximately 12 weeks for each participant, not including screening. Screening is required within 28 days prior to the start of the study. This study involves Part A (LY3143753) and Part B (LY3185643). Participants may only enroll in one part and at one dose level.

Official Title
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A Single-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3143753 and LY3185643 in Healthy Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: LY3143753 (Part A)
* Drug: LY3185643 (Part B)
* Drug: Placebo (Part A and Part B)
* Drug: rGlucagon (Part B)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overtly healthy males or females Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures Exclusion Criteria: Are investigator site personnel directly affiliated with this study and their immediate families Are currently enrolled in a clinical trial involving an investigational product (IP) or off-label use of a drug or device Have participated, within the last 3 months, in a clinical trial Have known or ongoing psychiatric disorders Show evidence of human immunodeficiency virus (HIV) infection 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 History of/current phaeochromocytoma History of/current insulinoma

Ages Eligible for Study
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Minimum Age: 18 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3143753 (Part A)<br>Single subcutaneous (SC) injection of ascending doses of LY3143753 on Day 1 | Drug: LY3143753 (Part A)<br>* Administered via SC injection<br>|
| Experimental: LY3185643 (Part B)<br>Single SC injection of ascending doses of LY3185643 on Day 1 | Drug: LY3185643 (Part B)<br>* Administered via SC injection<br>|
| Placebo Comparator: Placebo (Part A)<br>Single SC injection of normal saline on Day 1 | Drug: Placebo (Part A and Part B)<br>* Administered via SC injection<br>|
| Active Comparator: rGlucagon (Part B)<br>Single SC injection on Day 1 | Drug: rGlucagon (Part B)<br>* Administered via SC injection<br>|
| Placebo Comparator: Placebo (Part B)<br>Single SC injection of normal saline on Day 1 | Drug: Placebo (Part A and Part B)<br>* Administered via SC injection<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 other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section. | Baseline to Study Completion (Up to 84 Days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Drug Concentration (Cmax) of Part A |  | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours | 
| PK: Cmax of Part B |  | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours | 
| PK: Area Under the Concentration Curve From Zero to Infinity (AUC[0-∞]) of Part A |  | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours | 
| PK: AUC(0-∞) of Part B |  | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours | 
| PK: Time to Maximum Drug Concentration (Tmax) of Part A |  | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours | 
| PK: Tmax of Part B |  | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4, 6, 8 Hours | 
| Pharmacodynamic (PD): Absolute Maximum Blood Glucose of Part A |  | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours | 
| PD Absolute Maximum Blood Glucose of Part B |  | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours | 
| PD: Maximum Glucose Increase (Gmax) of Part A |  | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours | 
| PD: Gmax of Part B |  | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours | 
| PD: Time to Maximum Blood Glucose (Gtmax) of Part A |  | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours | 
| PD: Gtmax of Part B |  | Predose, 5,10, 15, 20, 25, 30, 35, 40, 45, 50, 550, 60, 70, 80, 90, 105, minutes and 2, 2.5, 3, 4 Hours | 
| QT Interval as Corrected by the Fridericia Method (QTcF) Change From Baseline of Part A |  | Baseline, 8 hours after drug administration | 
| QTcF Change From Baseline of Part B |  | Baseline, 8 hours after drug administration |