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

Hyperlipidemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01426412
• Other study ID #: 13980
• Secondary ID: I5S-EW-EFJA
• Status: Completed
• Phase: Phase 1
• Start date: September 2011
• Est. completion date: June 2013

Study information

• Verified date: January 2019
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

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

Related Conditions & MeSH terms

• Hyperlipidemia
• Hyperlipidemias
• Hyperlipoproteinemias

Intervention

Drug:
• LY3015014 IV
Administered IV over 30-90 minutes
• Placebo IV
Administered IV only over 30-90 minutes
• LY3015014 SC
Administered SC
• Placebo SC
Administered SC

Locations

Country	Name	City	State
United States	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.	Dallas	Texas
United States	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.	Glendale	California
United States	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.	Madison	Wisconsin

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Number of Participants With Detectable Levels of Anti-LY3015014 Antibodies		Days 8, 29 and 85