A Study of LY3015014 in Healthy Participants With High Cholesterol

Study Overview
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Brief Summary
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This is a study in healthy participants with high levels of bad cholesterol who are already taking a popular type of cholesterol-lowering medication called statins. Following multiple doses of LY3015014, investigators will study the safety and tolerability of the drug, how the body handles the drug, and the drug's effect on the body. Participants will remain in the study for about 3 months, not including screening. Screening is required within 28 days before the study starts.

Official Title
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A Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3015014 in Subjects With Elevated LDL-C on a Stable Statin Therapy

Conditions
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Healthy Volunteers, Hypercholesterolemia

Intervention / Treatment
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* Drug: LY3015014
* Drug: 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 Have body mass indexes of 18 to 35 kilograms per square meter (kg/m^2), inclusive, at screening Have screening low density lipoprotein-C (LDL-C) of between 100 and 180 milligrams per deciliter (mg/dL), inclusive, while having taken a stable dose of statin 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 post treatment hypersensitivity reactions [including but not limited to erythema multiforme major, linear immunoglobulin A (IgA) dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis] Have significant history of or current cardiovascular (excluding controlled hypertension), 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) of LY3015014<br>1.0 mg/kg of LY3015014 given subcutaneously (SQ) on 2 dosing occasions occurring 4 weeks apart (Q4W) (Days 1 and 29). | Drug: LY3015014<br>* Administered SQ<br>|
| Placebo Comparator: Placebo<br>0.9% sodium chloride injection given SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29). | Drug: Placebo<br>* Administered SQ<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 Other Non-Serious Adverse Events (AEs) or Any Serious AEs (SAEs) | Events deemed to be SAEs by the Investigator as related to study drug administration were collected during the study and 30 days following study drug administration. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. | Baseline through study completion (Day 127) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014 | The Cmax was calculated after each dose of LY3015014. | Day 1 and 29: 4 hours (h) and 24 h postdose | 
| PK: Area Under the Concentration Curve During One Dosing Interval (AUCt) of LY3015014 | The AUCt was calculated after each dose of LY3015014. | Day 1 and 29: 4 h and 24 h postdose | 
| PK: Time of Maximum Concentration (Tmax) of LY3015014 | tmax was calculated after each dosing of LY3015014 and is reported as the number of days for observed maximum concentration of LY3015014. | Day 1 and 29: 4 h and 24 h postdose | 
| Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | Percentage change from baseline in LDL-C was calculated as Least Squares (LS) mean using mixed model repeated measures (MMRM) analysis adjusted for baseline measurement. Treatment, day after dosing, and treatment-by-day interaction were included in the model. | Baseline, Day 43 and Day 57 |