A Study of LY3015014 in Otherwise Healthy Participants With High Low-density Lipoprotein (LDL) Cholesterol

Study Overview
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Brief Summary
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This is a phase 1 study in otherwise healthy participants with high LDL cholesterol. Following multiple doses of LY3015014, the safety and tolerability of the drug, how the body handles the drug, and the drug's effect on the body will be evaluated. Participants will participate in the study for approximately 3 months not including screening. Screening is required within 42 days prior to the start of the study.

Official Title
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A Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3015014 in Japanese and Non-Japanese Subjects With Elevated LDL-C

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: LY3015014
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must be healthy males or females without childbearing potential as determined by medical history and physical examination, including first-generation Japanese participants Have body mass indexes of 18 to 35 kilograms per meter square (kg/m^2), inclusive, at screening Have screening low-density lipoprotein cholesterol (LDL-C) of between 100 and 180 milligrams per deciliter (mg/dL), inclusive Exclusion Criteria: Have known allergies to compounds related to LY3015014 or any components of the formulation or known clinically significant hypersensitivity to biologic agents Have a history of atopy, significant allergies to humanized monoclonal antibodies, clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe posttreatment hypersensitivity reactions [including but not limited to erythema multiforme major, linear immunoglobulin (Ig)A dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis) Have significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs, of constituting a risk when taking the study medication, or of interfering with the interpretation of data Have received any vaccine(s) within 1 month of LY3015014 dosing or intend to do so during 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

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1.0 milligrams per kilogram (mg/kg) LY3015014 Every 2 Weeks<br>1.0 mg/kg LY3015014 given subcutaneously (SC) once every 2 weeks for 29 days. | Drug: LY3015014<br>* Administered SC<br>|
| Experimental: 1.0 mg/kg LY3015014 Every 4 Weeks<br>1.0 mg/kg LY3015014 given SC once every 4 weeks for 29 days. | Drug: LY3015014<br>* Administered SC<br>|
| Experimental: 3.0 mg/kg LY3015014 Every 2 Weeks<br>3.0 mg/kg LY3015014 given SC once every 2 weeks for 29 days. | Drug: LY3015014<br>* Administered SC<br>|
| Experimental: 3.0 mg/kg LY3015014 Every 4 Weeks<br>3.0 mg/kg LY3015014 given SC once every 4 weeks for 29 days. | Drug: LY3015014<br>* Administered SC<br>|
| Placebo Comparator: Placebo Every 2 Weeks<br>Saline injection (to match LY3015014) given SC once every 2 weeks for 29 days. | Other: Placebo<br>* Administered SC<br>|
| Placebo Comparator: Placebo Every 4 Weeks<br>Saline injection (to match LY3015014) given SC once every 4 weeks for 29 days. | Other: Placebo<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 1 or More Drug Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAEs) | TEAEs were defined as SAEs and other non-serious AEs that occurred or worsened after study treatment. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events section of this report. | Baseline through study completion (up to Day 127) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014 | The Cmax following the first dose and last dose of LY3015014 is reported. | First Dose (Day 1) and Last Dose (Day 29): Predose, 4 Hours and 24 Hours Postdose | 
| PK: Area Under the Concentration Curve of LY3015014 During 1 Dosing Interval (AUC[0-tau]) | The AUC(0-tau) following the first dose and last dose of LY3015014 is reported. | First Dose (Day 1) and Last Dose (Day 29): Predose, 4 Hours and 24 Hours Postdose | 
| PK: Time of Maximum Concentration (Tmax) of LY3015014 | The tmax following the first dose and last dose of LY3015014 is reported. | First Dose: Predose (Day 1) up to Week 4 postdose and Last Dose: predose (Day 29) up to Week 14 postdose | 
| Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Percent change from baseline in LDL-C was calculated as Least Squares (LS) mean using mixed effect model repeated measures (MMRM) analysis adjusted for baseline measurement, treatment, day after dosing, and treatment by day interaction. | Baseline, Day 43, Day 57, and Day 127 |