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

A Single-Dose, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of LY3015014 in Subjects With Elevated LDL-C

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.

Study Overview

• Status: Completed
• Conditions: Hyperlipidemia
• Intervention / Treatment: Drug: Placebo SC; Drug: LY3015014 IV; Drug: Placebo IV; Drug: LY3015014 SC

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • 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.
  • Texas
    • Dallas, Texas, United States, 75247
      • 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.
  • Wisconsin
    • Madison, Wisconsin, United States, 53704
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LY3015014 intravenously (IV); A single dose of LY3015014 up to 10.0 milligrams per kilogram (mg/kg) administered IV	Drug: LY3015014 IV; Administered IV over 30-90 minutes
Experimental: LY3015014 IV Japanese; Single dose of LY3015014 10.0 mg/kg administered IV to Japanese participants. Added per protocol amendment effective October, 2012.	Drug: LY3015014 IV; Administered IV over 30-90 minutes
Placebo Comparator: Placebo IV; Administered IV once only	Drug: Placebo IV; Administered IV only over 30-90 minutes
Experimental: LY3015014 subcutaneously (SC); A single dose of LY3015014 up to 3.0 mg/kg administered SC	Drug: LY3015014 SC; Administered SC
Experimental: LY3015014 SC + Statin; A single dose of LY3015014 up to 3 mg/kg administered SC in addition to participant's dose of statin	Drug: LY3015014 SC; Administered SC
Placebo Comparator: Placebo SC; Administered SC once only	Drug: Placebo SC; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Clinically Significant Effects	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.	Baseline to study completion (up to 22 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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.	Baseline, Days 15 and 29
Number of Participants With Detectable Levels of Anti-LY3015014 Antibodies		Days 8, 29 and 85

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: August 29, 2011
• First Submitted That Met QC Criteria: August 29, 2011
• First Posted (Estimate): August 31, 2011

Study Record Updates

• Last Update Posted (Actual): April 5, 2019
• Last Update Submitted That Met QC Criteria: January 7, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Dyslipidemias; Hyperlipidemias; Physiological Effects of Drugs; Immunologic Factors; Antibodies, Monoclonal
• Other Study ID Numbers: 13980; I5S-EW-EFJA (Other Identifier: Eli Lilly and Company)