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

Lilly

Status and phase: Completed; Phase 1

Conditions: Hyperlipidemia

Treatments: Drug: LY3015014 SC; Drug: Placebo IV; Drug: LY3015014 IV; Drug: Placebo SC

Study type: Interventional

Funder types: Industry

Identifiers

NCT01426412

13980

I5S-EW-EFJA (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 69 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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69 participants in 6 patient groups, including a placebo group

LY3015014 intravenously (IV)

Experimental group

Description:

A single dose of LY3015014 up to 10.0 milligrams per kilogram (mg/kg) administered IV

Treatment:

Drug: LY3015014 IV

LY3015014 IV Japanese

Experimental group

Description:

Single dose of LY3015014 10.0 mg/kg administered IV to Japanese participants. Added per protocol amendment effective October, 2012.

Treatment:

Drug: LY3015014 IV

Placebo IV

Placebo Comparator group

Description:

Administered IV once only

Treatment:

Drug: Placebo IV

LY3015014 subcutaneously (SC)

Experimental group

Description:

A single dose of LY3015014 up to 3.0 mg/kg administered SC

Treatment:

Drug: LY3015014 SC

LY3015014 SC + Statin

Experimental group

Description:

A single dose of LY3015014 up to 3 mg/kg administered SC in addition to participant's dose of statin

Treatment:

Drug: LY3015014 SC

Placebo SC

Placebo Comparator group

Description:

Administered SC once only

Treatment:

Drug: Placebo SC