A Study of LY3084077 in Healthy Participants

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the safety and tolerability of the study drug known as LY3084077 in healthy participants. The study will also investigate how much of the study drug gets into the blood stream and how long it takes the body to get rid of it. Information about any side effects that may occur will also be collected. The study is expected to last approximately 8 weeks for each participant.

Official Title
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A Single-Dose, Dose-Escalation Study to Determine the Safety, Tolerability, and Pharmacokinetics of LY3084077 in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: Placebo
* Drug: LY3084077


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have normal blood pressure Must be a healthy male or female who cannot become pregnant Have a body mass index (BMI) of 18.5 to 40.0 kg/m^2, inclusive, at screening Exclusion Criteria: Have known allergies to fibroblast growth factor-21 (FGF21) analogues, glucagon-like peptide-1 (GLP1), GLP1-analogues or other related compounds Have previous exposure to FGF21 analogues or GLP1 analogues Have received live vaccine(s) within 1 month of screening, or intend to during the study Have previously completed or withdrawn from this study Have or used to have health problems or laboratory test results or electrocardiogram (ECG) readings that in the opinion of the doctor, could make it unsafe to participate, or interfere with understanding the results of the study Have received treatment with biologic agents (such as monoclonal antibodies) within 3 months or 5 half-lives (whichever is longer) prior to dosing Have problems with the immune system, due to a disease or treatment Have a personal or family history of medullary thyroid carcinoma (MTC) or have multiple endocrine neoplasia syndrome type 2 Have a history of pancreatitis

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Single dose of placebo matching LY3084077 administered subcutaneously (SC). | Drug: Placebo<br>* Given as a SC injection.<br>|
| Experimental: LY3084077<br>Single escalating doses (1 mg up to 300 mg) of LY3084077 administered SC. | Drug: LY3084077<br>* Given as a 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 | An SAE is an adverse event that results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. A summary of other non-serious adverse events and all serious adverse events, regardless of causality, is located in the Reported Adverse Events Section. | Pre-dose, Up to Day 190 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Curve Zero to Infinity (AUC[0-∞]) GLP1-Fc Domain of LY3084077 |  | Day 1 and Day 29: Predose, 2,4,8,12,24,36,48,72,96,120,168,336 hours post dose | 
| PK: Maximum Concentration (Cmax) GLP1-Fc Domain of LY3084077 |  | Day 1 and Day 29: Predose, 2,4,8,12,24,36,48,72,96,120,168,336 hours post dose | 
| Pharmacodynamics (PD): Percent Change From Baseline in Fasting Triglycerides | Percent change=(measure at time t-measure at baseline)/measure at baseline*100%). Least Square Means (LS means) were calculated using MMRM analysis adjusting for the random effect of participant, effect of baseline, and fixed categorical effects of treatment, visit, and treatment-by-visit interaction. | Baseline, Up to Day 15 | 
| PD: Change From Baseline in Fasting Insulin | LS means were calculated using MMRM analysis adjusting for the random effect of participant, effect of baseline, and fixed categorical effects of treatment, visit, and treatment-by-visit interaction. | Baseline, Up to Day 15 | 
| PD: Change From Baseline in Weight |  | Baseline, Up to Day 15 | 
| PD: Change From Baseline Up to Day 2 in Level of C-peptide AUC (Predose to 4 Hours) After a Standard Meal | LS means were calculated using MMRM analysis adjusting for the random effect of participant, effect of baseline, and fixed categorical effects of treatment, visit, and treatment-by-visit interaction. | Baseline, Day 2 | 
| PD: Change From Baseline to Day 2 Incremental AUC Level of Blood Glucose (Predose to 6 Hours) After a Standard Meal | LS means were calculated using MMRM analysis adjusting for the random effect of participant, effect of baseline, and fixed categorical effects of treatment, visit, and treatment-by-visit interaction. | Baseline, Day 2 | 
| PD: Change From Baseline to Day 2 in Fasting Glucagon | LS means were calculated using MMRM analysis adjusting for the random effect of participant, effect of baseline, and fixed categorical effects of treatment, visit, and treatment-by-visit interaction. | Baseline, Up to Day 2 | 
| Number of Participants Developing Anti-LY3084077 Antibodies | The number of participants with 1:4 baseline and postbaseline positive anti-LY3084077 antibody titers. | Pre-dose, Up to Day 190 |