A Study of LY3015014 in Healthy Participants With Elevated Low Density Lipoprotein Cholesterol

Phase 1

Completed

Interventions: Drug: Placebo SC
Drug: LY3015014 IV
Drug: Placebo IV
Drug: LY3015014 SC

Brief Summary: This is a study in otherwise healthy Japanese and non-Japanese participants with elevated low density lipoprotein cholesterol (LDL-C). Following single 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 remain in the study for approximately up to 6 months.

Recruitment & Eligibility

Inclusion Criteria

Are overtly healthy males or females, as determined by medical history and physical examination
To qualify as Japanese for the purpose of this study, the participant must be first-generation Japanese, defined as the participant's biological parents and all of the participant's biological grandparents must be of exclusive Japanese descent, and must have been born in Japan. Japanese participants have to be between the ages of 20-65, inclusive, at screening
Statin naive participants, have a screening LDL-C of between 100 and 180 milligrams per deciliter (mg/dL), inclusive; for participants currently taking a statin, have a screening LDL-C of between 100 and 160 mg/dL
Have serum triglycerides <400 mg/dL

Additional inclusion criteria for participants in the statin-interaction cohort:

At screening, must have been on a stable dose of either atorvastatin [10 to 40 mg once daily (QD)], rosuvastatin (5 to 20 mg QD), simvastatin (20 to 40 mg QD), lovastatin (40 to 80 mg QD), or pravastatin (40 to 80 mg QD) which has been well tolerated for at least 3 months

Exclusion Criteria

Have known allergies to compounds related to LY3015014 or any components of the formulation, or known clinically significant hypersensitivity to biologic agents, or known allergies to acetaminophen and/or antihistamines
Intend to use over-the-counter or prescription medication within 14 days prior to dosing (excluding the statins listed in Inclusion Criterion), other than estrogen/progesterone as hormone replacement therapy (HRT) and thyroid medications. Participants taking these medications should be on chronic, stable doses. Certain medications, for example vitamin supplements, may be permitted at the discretion of the investigator and the sponsor. Participants on statins may be allowed to be on a stable dose of single hypertensive agent if agreed upon by sponsor and investigator
Have received any vaccine(s) within 1 month of LY3015014 dosing, or intend to 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
Have a history of atopy, or significant allergies to humanized monoclonal antibodies, or clinically significant multiple or severe drug allergies, or intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions [including, but not limited to, erythema multiforme major, linear immunoglobulin (Ig)A dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis]

Additional exclusion criteria for participants in the statin-interaction cohort:

Incidence of unexplained muscle pain, or incidence of frequent muscle cramp within the last 6 months

Arm && Interventions

Group	Intervention	Description
Placebo SC	Placebo SC	Administered SC once only
LY3015014 intravenously (IV)	LY3015014 IV	A single dose of LY3015014 up to 10.0 milligrams per kilogram (mg/kg) administered IV
LY3015014 IV Japanese	LY3015014 IV	Single dose of LY3015014 10.0 mg/kg administered IV to Japanese participants. Added per protocol amendment effective October, 2012.
Placebo IV	Placebo IV	Administered IV once only
LY3015014 subcutaneously (SC)	LY3015014 SC	A single dose of LY3015014 up to 3.0 mg/kg administered SC
LY3015014 SC + Statin	LY3015014 SC	A single dose of LY3015014 up to 3 mg/kg administered SC in addition to participant's dose of statin

Primary Outcome Measures

Name	Time	Method
Number of Participants With Clinically Significant Effects	Baseline to study completion (up to 22 weeks)	Adverse events (AEs) were considered as clinically significant effects. A summary of serious AEs (SAEs) and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events module.

Secondary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Area Under the Concentration-Time Curve From Time 0 to the Last Time Point With a Measurable Concentration of LY3015014 [AUC(0-tlast)]	Predose, 0, 1, 2, 4, 12, 24 hours post dose, and 3, 5, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85, 99, 113, 127 and 155 days post-dose
PK: Maximum Concentration (Cmax) of LY3015014	Predose, 0, 1, 2, 4, 12, 24 hours post dose, and 3, 5, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 85, 99, 113, 127 and 155 days post-dose
Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)	Baseline, Days 15 and 29	Least Square means were calculated using mixed-effects models for repeated measures analysis. The model included factors for treatment, visits and baseline LDL-C. Percent change = (LDL value on Days 15 or 29 - LDL at baseline) / LDL at baseline \*100.
Number of Participants With Detectable Levels of Anti-LY3015014 Antibodies	Days 8, 29 and 85

Locations (1): For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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Madison, Wisconsin, United States