Healthy Volunteers
Conditions
Brief summary
This is a phase 1 study in otherwise healthy participants with high LDL cholesterol. Following multiple 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 participate in the study for approximately 3 months not including screening. Screening is required within 42 days prior to the start of the study.
Interventions
DRUGLY3015014
Administered SC
OTHERPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants must be healthy males or females without childbearing potential as determined by medical history and physical examination, including first-generation Japanese participants * Have body mass indexes of 18 to 35 kilograms per meter square (kg/m\^2), inclusive, at screening * Have screening low-density lipoprotein cholesterol (LDL-C) of between 100 and 180 milligrams per deciliter (mg/dL), inclusive
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 posttreatment hypersensitivity reactions \[including but not limited to erythema multiforme major, linear immunoglobulin (Ig)A dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis) * Have significant history of or current cardiovascular, 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 1 or More Drug Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAEs) | Baseline through study completion (up to Day 127) | TEAEs were defined as SAEs and other non-serious AEs that occurred or worsened after study treatment. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events section of this report. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014 | First Dose (Day 1) and Last Dose (Day 29): Predose, 4 Hours and 24 Hours Postdose | The Cmax following the first dose and last dose of LY3015014 is reported. |
| PK: Area Under the Concentration Curve of LY3015014 During 1 Dosing Interval (AUC[0-tau]) | First Dose (Day 1) and Last Dose (Day 29): Predose, 4 Hours and 24 Hours Postdose | The AUC(0-tau) following the first dose and last dose of LY3015014 is reported. |
| PK: Time of Maximum Concentration (Tmax) of LY3015014 | First Dose: Predose (Day 1) up to Week 4 postdose and Last Dose: predose (Day 29) up to Week 14 postdose | The tmax following the first dose and last dose of LY3015014 is reported. |
| Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Baseline, Day 43, Day 57, and Day 127 | Percent change from baseline in LDL-C was calculated as Least Squares (LS) mean using mixed effect model repeated measures (MMRM) analysis adjusted for baseline measurement, treatment, day after dosing, and treatment by day interaction. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 1.0 mg/kg LY3015014 Q2W LY3015014: 1.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | 12 |
| 1.0 mg/kg LY3015014 Q4W LY3015014: 1.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | 10 |
| 3.0 mg/kg LY3015014 Q2W LY3015014: 3.0 mg/kg given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | 11 |
| 3.0 mg/kg LY3015014 Q4W LY3015014: 3.0 mg/kg given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | 9 |
| Placebo Q2W Placebo given as SC injection Q2W on Days 1, 15, and 29 for a total of 3 doses. | 5 |
| Placebo Q4W Placebo given as SC injection Q4W on Days 1 and 29 for a total of 2 doses. | 4 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 2 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | 1.0 mg/kg LY3015014 Q2W | 1.0 mg/kg LY3015014 Q4W | 3.0 mg/kg LY3015014 Q2W | 3.0 mg/kg LY3015014 Q4W | Placebo Q2W | Placebo Q4W | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 52.0 years STANDARD_DEVIATION 8 | 46.8 years STANDARD_DEVIATION 10.3 | 53.7 years STANDARD_DEVIATION 11.6 | 51.4 years STANDARD_DEVIATION 13.6 | 49.2 years STANDARD_DEVIATION 13.2 | 47.8 years STANDARD_DEVIATION 15.2 | 50.6 years STANDARD_DEVIATION 11.1 |
| Baseline Low-Density Lipoprotein Cholesterol (LDL-C) | 139.6 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 26.1 | 119.3 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 48.1 | 141.8 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 20.2 | 151.7 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 30.6 | 165.0 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 28.9 | 122.7 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 36 | 139.4 milligrams per deciliter (mg/dL) STANDARD_DEVIATION 33.8 |
| Race/Ethnicity, Customized Asian | 5 Participants | 4 Participants | 3 Participants | 3 Participants | 1 Participants | 0 Participants | 16 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 17 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 3 Participants | 5 Participants | 4 Participants | 1 Participants | 1 Participants | 17 Participants |
| Region of Enrollment United States | 12 Participants | 10 Participants | 11 Participants | 9 Participants | 5 Participants | 4 Participants | 51 Participants |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 9 Participants | 3 Participants | 2 Participants | 2 Participants | 25 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 2 Participants | 6 Participants | 3 Participants | 2 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 7 / 12 | 6 / 10 | 8 / 11 | 7 / 9 | 3 / 5 | 0 / 4 |
| serious Total, serious adverse events | 0 / 12 | 0 / 10 | 0 / 11 | 0 / 9 | 0 / 5 | 0 / 4 |
Outcome results
Primary
Number of Participants With 1 or More Drug Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAEs)
TEAEs were defined as SAEs and other non-serious AEs that occurred or worsened after study treatment. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events section of this report.
Time frame: Baseline through study completion (up to Day 127)
Population: All enrolled participants who received at least 1 dose of study drug (LY3015014 or placebo).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 1.0 mg/kg LY3015014 Q2W | Number of Participants With 1 or More Drug Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAEs) | 1 or More TEAEs Related to Study Drug | 4 Participants |
| 1.0 mg/kg LY3015014 Q2W | Number of Participants With 1 or More Drug Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAEs) | Any SAEs | 0 Participants |
| 1.0 mg/kg LY3015014 Q4W | Number of Participants With 1 or More Drug Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAEs) | 1 or More TEAEs Related to Study Drug | 3 Participants |
| 1.0 mg/kg LY3015014 Q4W | Number of Participants With 1 or More Drug Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAEs) | Any SAEs | 0 Participants |
| 3.0 mg/kg LY3015014 Q2W | Number of Participants With 1 or More Drug Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAEs) | 1 or More TEAEs Related to Study Drug | 5 Participants |
| 3.0 mg/kg LY3015014 Q2W | Number of Participants With 1 or More Drug Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAEs) | Any SAEs | 0 Participants |
| 3.0 mg/kg LY3015014 Q4W | Number of Participants With 1 or More Drug Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAEs) | Any SAEs | 0 Participants |
| 3.0 mg/kg LY3015014 Q4W | Number of Participants With 1 or More Drug Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAEs) | 1 or More TEAEs Related to Study Drug | 2 Participants |
| Placebo Q2W Plus Placebo Q4W | Number of Participants With 1 or More Drug Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAEs) | 1 or More TEAEs Related to Study Drug | 3 Participants |
| Placebo Q2W Plus Placebo Q4W | Number of Participants With 1 or More Drug Related Treatment-Emergent Adverse Events (TEAEs) or Any Serious AEs (SAEs) | Any SAEs | 0 Participants |
Secondary
Percent Change From Baseline to Days 43, 57, and 127 in LDL-C
Percent change from baseline in LDL-C was calculated as Least Squares (LS) mean using mixed effect model repeated measures (MMRM) analysis adjusted for baseline measurement, treatment, day after dosing, and treatment by day interaction.
Time frame: Baseline, Day 43, Day 57, and Day 127
Population: Randomized participants who received at least 1 dose of study drug (LY3015014 or placebo) and had a baseline and at least 1 postbaseline measurement for LDL-C.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 1.0 mg/kg LY3015014 Q2W | Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Day 43 | -49.76 percentage of change |
| 1.0 mg/kg LY3015014 Q2W | Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Day 127 | -7.52 percentage of change |
| 1.0 mg/kg LY3015014 Q2W | Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Day 57 | -47.01 percentage of change |
| 1.0 mg/kg LY3015014 Q4W | Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Day 57 | -44.41 percentage of change |
| 1.0 mg/kg LY3015014 Q4W | Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Day 43 | -47.56 percentage of change |
| 1.0 mg/kg LY3015014 Q4W | Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Day 127 | -15.09 percentage of change |
| 3.0 mg/kg LY3015014 Q2W | Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Day 57 | -44.20 percentage of change |
| 3.0 mg/kg LY3015014 Q2W | Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Day 43 | -45.20 percentage of change |
| 3.0 mg/kg LY3015014 Q2W | Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Day 127 | -23.39 percentage of change |
| 3.0 mg/kg LY3015014 Q4W | Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Day 43 | -46.64 percentage of change |
| 3.0 mg/kg LY3015014 Q4W | Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Day 127 | -18.91 percentage of change |
| 3.0 mg/kg LY3015014 Q4W | Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Day 57 | -56.80 percentage of change |
| Placebo Q2W Plus Placebo Q4W | Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Day 57 | -12.16 percentage of change |
| Placebo Q2W Plus Placebo Q4W | Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Day 43 | 0.16 percentage of change |
| Placebo Q2W Plus Placebo Q4W | Percent Change From Baseline to Days 43, 57, and 127 in LDL-C | Day 127 | -0.99 percentage of change |
p-value: <0.00190% CI: [-63.84, -35.99]Mixed Effects Model Analysis
p-value: <0.00190% CI: [-48.78, -20.93]Mixed Effects Model Analysis
p-value: <0.00190% CI: [-62.1, -33.34]Mixed Effects Model Analysis
p-value: <0.00190% CI: [-46.69, -17.82]Mixed Effects Model Analysis
p-value: <0.00190% CI: [-60.07, -30.64]Mixed Effects Model Analysis
p-value: <0.00190% CI: [-46.76, -17.32]Mixed Effects Model Analysis
p-value: <0.00190% CI: [-61.12, -32.49]Mixed Effects Model Analysis
p-value: <0.00190% CI: [-58.95, -30.32]Mixed Effects Model Analysis
p-value: 0.4490% CI: [-20.51, 7.44]Mixed Effect Model Analysis
p-value: 0.10890% CI: [-28.53, 0.33]Mixed Effect Model Analysis
p-value: 0.01390% CI: [-37.13, -7.69]Mixed Effect Model Analysis
p-value: 0.04290% CI: [-32.42, -3.44]Mixed Effect Model Analysis
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014
The Cmax following the first dose and last dose of LY3015014 is reported.
Time frame: First Dose (Day 1) and Last Dose (Day 29): Predose, 4 Hours and 24 Hours Postdose
Population: All randomized participants who received at least 1 dose of LY3015014 and had evaluable Cmax data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.0 mg/kg LY3015014 Q2W | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014 | First Dose | 4.24 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 59 |
| 1.0 mg/kg LY3015014 Q2W | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014 | Last Dose | 9.21 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 38 |
| 1.0 mg/kg LY3015014 Q4W | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014 | Last Dose | 6.64 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 31 |
| 1.0 mg/kg LY3015014 Q4W | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014 | First Dose | 4.82 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 53 |
| 3.0 mg/kg LY3015014 Q2W | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014 | Last Dose | 35.1 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 24 |
| 3.0 mg/kg LY3015014 Q2W | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014 | First Dose | 14.6 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 48 |
| 3.0 mg/kg LY3015014 Q4W | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014 | Last Dose | 23.1 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 51 |
| 3.0 mg/kg LY3015014 Q4W | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014 | First Dose | 17.9 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 61 |
Secondary
PK: Area Under the Concentration Curve of LY3015014 During 1 Dosing Interval (AUC[0-tau])
The AUC(0-tau) following the first dose and last dose of LY3015014 is reported.
Time frame: First Dose (Day 1) and Last Dose (Day 29): Predose, 4 Hours and 24 Hours Postdose
Population: All randomized participants who received at least 1 dose of LY3015014 and had evaluable AUC(0-tau) data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.0 mg/kg LY3015014 Q2W | PK: Area Under the Concentration Curve of LY3015014 During 1 Dosing Interval (AUC[0-tau]) | First Dose | 1080 micrograms*hours/milliliter (µg*h/mL) | Geometric Coefficient of Variation 51 |
| 1.0 mg/kg LY3015014 Q2W | PK: Area Under the Concentration Curve of LY3015014 During 1 Dosing Interval (AUC[0-tau]) | Last Dose | 2450 micrograms*hours/milliliter (µg*h/mL) | Geometric Coefficient of Variation 35 |
| 1.0 mg/kg LY3015014 Q4W | PK: Area Under the Concentration Curve of LY3015014 During 1 Dosing Interval (AUC[0-tau]) | Last Dose | 2810 micrograms*hours/milliliter (µg*h/mL) | Geometric Coefficient of Variation 24 |
| 1.0 mg/kg LY3015014 Q4W | PK: Area Under the Concentration Curve of LY3015014 During 1 Dosing Interval (AUC[0-tau]) | First Dose | 2110 micrograms*hours/milliliter (µg*h/mL) | Geometric Coefficient of Variation 37 |
| 3.0 mg/kg LY3015014 Q2W | PK: Area Under the Concentration Curve of LY3015014 During 1 Dosing Interval (AUC[0-tau]) | First Dose | 3890 micrograms*hours/milliliter (µg*h/mL) | Geometric Coefficient of Variation 47 |
| 3.0 mg/kg LY3015014 Q2W | PK: Area Under the Concentration Curve of LY3015014 During 1 Dosing Interval (AUC[0-tau]) | Last Dose | 9440 micrograms*hours/milliliter (µg*h/mL) | Geometric Coefficient of Variation 17 |
| 3.0 mg/kg LY3015014 Q4W | PK: Area Under the Concentration Curve of LY3015014 During 1 Dosing Interval (AUC[0-tau]) | First Dose | 8230 micrograms*hours/milliliter (µg*h/mL) | Geometric Coefficient of Variation 52 |
| 3.0 mg/kg LY3015014 Q4W | PK: Area Under the Concentration Curve of LY3015014 During 1 Dosing Interval (AUC[0-tau]) | Last Dose | 10900 micrograms*hours/milliliter (µg*h/mL) | Geometric Coefficient of Variation 44 |
Secondary
PK: Time of Maximum Concentration (Tmax) of LY3015014
The tmax following the first dose and last dose of LY3015014 is reported.
Time frame: First Dose: Predose (Day 1) up to Week 4 postdose and Last Dose: predose (Day 29) up to Week 14 postdose
Population: All randomized participants who received at least 1 dose of LY3015014 and had evaluable tmax data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 1.0 mg/kg LY3015014 Q2W | PK: Time of Maximum Concentration (Tmax) of LY3015014 | First Dose | 4 days |
| 1.0 mg/kg LY3015014 Q2W | PK: Time of Maximum Concentration (Tmax) of LY3015014 | Last Dose | 5 days |
| 1.0 mg/kg LY3015014 Q4W | PK: Time of Maximum Concentration (Tmax) of LY3015014 | Last Dose | 5 days |
| 1.0 mg/kg LY3015014 Q4W | PK: Time of Maximum Concentration (Tmax) of LY3015014 | First Dose | 4 days |
| 3.0 mg/kg LY3015014 Q2W | PK: Time of Maximum Concentration (Tmax) of LY3015014 | Last Dose | 5 days |
| 3.0 mg/kg LY3015014 Q2W | PK: Time of Maximum Concentration (Tmax) of LY3015014 | First Dose | 4 days |
| 3.0 mg/kg LY3015014 Q4W | PK: Time of Maximum Concentration (Tmax) of LY3015014 | First Dose | 4 days |
| 3.0 mg/kg LY3015014 Q4W | PK: Time of Maximum Concentration (Tmax) of LY3015014 | Last Dose | 5 days |