A Study of LY3475766 in Healthy Participants

Study Overview
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Brief Summary
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This study will evaluate the safety and tolerability of LY3475766 when given to participants with high levels of blood fat called triglycerides. It will also investigate how the body processes the study drug and the effect of the study drug on the body. Information about any side effects will be documented. This study will last up to 16 weeks for each participant.

Official Title
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A Randomized, Double-Blind, Single Dose, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3475766

Conditions
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Dyslipidemias

Intervention / Treatment
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* Drug: LY3475766 - IV
* Drug: LY3475766 - SC
* Drug: Placebo - IV
* Drug: Placebo - SC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are overtly healthy males or females, apart from dyslipidemia Male participants must agree to adhere to contraception restrictions Female participants must be of nonchildbearing potential and include those who are infertile due to surgical sterilization or those who are postmenopausal Have a body mass index (BMI) >18.5 and <40 kilograms per meter squared (kg/m²) Have clinical laboratory test results within normal reference range, or acceptable deviations per investigator discretion Have a fasting triglyceride (TG) level that is 135 to 499 milligrams per deciliter (mg/dL), inclusive, at both screening and Day -1 Have a fasting low density lipoprotein cholesterol (LDL-C) level greater than or equal to (≥) 70 mg/dL, inclusive, at screening and Day -1 Have had a stable body weight for the 3 months prior to randomization (<5% body weight change) Have not modified diet or adopted any nutritional lifestyle modification within 3 months prior to randomization Exclusion Criteria: Are taking or have started taking Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors within 3 months prior to randomization; or statins, fibrates, or niacin ≤1000 mg/day within 8 weeks prior to randomization; or niacin >1000 milligrams per day (mg/day) within 16 weeks prior to randomization; or any other lipid-lowering agents within 1 month prior to randomization Are taking or have started taking a beta-blocker, antiarrhythmic, non-dihydropyridine calcium channel blocker, ivabradine, or any other heart rate lowering agent within 1 month or 5 half-lives prior to randomization, whichever is longer Have a diagnosis of diabetes mellitus (type 1 diabetes mellitus or type 2 diabetes mellitus) or have 1 of the following at screening: fasting plasma glucose concentration ≥126 mg/dL (7.0 millimoles per liter [mmol/L]) OR a glycated hemoglobin level ≥6.5% (48 millimoles per mole [mmol/mol]) Have previously completed or withdrawn from this study or any other study investigating LY3475766, and have previously received the investigational product Have known allergies to LY3475766, related compounds, or any components of the formulation, or history of significant atopy Have a seated heart rate ≤50 beats per minute Have clinically significant abnormal electrocardiogram (ECG) results constituting a risk while taking the investigational product, as determined by the investigator Have an abnormal blood pressure (BP) as determined by the investigator

Ages Eligible for Study
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Minimum Age: 18 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: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LY3475766 - IV<br>LY3475766 administered intravenously (IV) to participants with dyslipidemia | Drug: LY3475766 - IV<br>* Administered IV<br>|
| Placebo Comparator: Placebo - IV<br>Placebo administered IV to participants with dyslipidemia | Drug: Placebo - IV<br>* Administered IV<br>|
| Experimental: LY3475766 - SC<br>LY3475766 administered subcutaneously (SC) to participants with dyslipidemia | Drug: LY3475766 - SC<br>* Administered SC<br>|
| Placebo Comparator: Placebo - SC<br>Placebo administered SC to participants with dyslipidemia | Drug: Placebo - SC<br>* Administered SC<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 Day 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of LY3475766 | PK: AUC of LY3475766 | Predose up to Day 85 | 
| PK: Maximum Observed Drug Concentration (Cmax) of LY3475766 | PK: Cmax of LY3475766 | Predose up to Day 85 | 
| PK: Time to Maximum Observed Drug Concentration (Tmax) of LY3475766 | PK: Tmax of LY3475766 | Predose up to Day 85 | 
| Pharmacodynamics (PD): Percent Change from Baseline in Triglycerides (TG) | PD: Percent Change from Baseline in TG | Baseline, Day 85 | 
| PD: Percent Change from Baseline in Low-Density Lipoprotein Cholesterol (LDL-C) | PD: Percent Change from Baseline in LDL-C | Baseline, Day 85 | 
| PD: Percent Change from Baseline in Apolipoprotein B (ApoB) | PD: Percent Change from Baseline in ApoB | Baseline, Day 85 |