Healthy Volunteers, Hypercholesterolemia
Conditions
Brief summary
This is a study in healthy participants with high levels of bad cholesterol who are already taking a popular type of cholesterol-lowering medication called statins. Following multiple doses of LY3015014, investigators will study the safety and tolerability of the drug, how the body handles the drug, and the drug's effect on the body. Participants will remain in the study for about 3 months, not including screening. Screening is required within 28 days before the study starts.
Interventions
DRUGLY3015014
Administered SQ
DRUGPlacebo
Administered SQ
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 * Have body mass indexes of 18 to 35 kilograms per square meter (kg/m\^2), inclusive, at screening * Have screening low density lipoprotein-C (LDL-C) of between 100 and 180 milligrams per deciliter (mg/dL), inclusive, while having taken a stable dose of statin
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 post treatment hypersensitivity reactions \[including but not limited to erythema multiforme major, linear immunoglobulin A (IgA) dermatosis, toxic epidermal necrolysis, or exfoliative dermatitis\] * Have significant history of or current cardiovascular (excluding controlled hypertension), 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 One or More Other Non-Serious Adverse Events (AEs) or Any Serious AEs (SAEs) | Baseline through study completion (Day 127) | Events deemed to be SAEs by the Investigator as related to study drug administration were collected during the study and 30 days following study drug administration. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014 | Day 1 and 29: 4 hours (h) and 24 h postdose | The Cmax was calculated after each dose of LY3015014. |
| PK: Area Under the Concentration Curve During One Dosing Interval (AUCt) of LY3015014 | Day 1 and 29: 4 h and 24 h postdose | The AUCt was calculated after each dose of LY3015014. |
| PK: Time of Maximum Concentration (Tmax) of LY3015014 | Day 1 and 29: 4 h and 24 h postdose | tmax was calculated after each dosing of LY3015014 and is reported as the number of days for observed maximum concentration of LY3015014. |
| Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | Baseline, Day 43 and Day 57 | Percentage change from baseline in LDL-C was calculated as Least Squares (LS) mean using mixed model repeated measures (MMRM) analysis adjusted for baseline measurement. Treatment, day after dosing, and treatment-by-day interaction were included in the model. |
Countries
United States
Participant flow
Pre-assignment details
Participants who discontinued from the study prior to completion were permitted to be replaced.
Participants by arm
| Arm | Count |
|---|---|
| 1.0 mg/kg of LY3015014 LY3015014: 1.0 mg/kg of LY3015014 SQ on 2 dosing occasions (Q4W) (Days 1 and 29). | 11 |
| Placebo Placebo: 0.9% sodium chloride injection SQ (to match LY3015014) on 2 dosing occasions Q4W (Days 1 and 29). | 2 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | 1.0 mg/kg of LY3015014 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 55.0 years STANDARD_DEVIATION 6.3 | 52.0 years STANDARD_DEVIATION 4.2 | 54.5 years STANDARD_DEVIATION 6 |
| Baseline Low Density Lipoprotein (LDL)-C | 134.430 milligrams/deciliter (mg/dL) STANDARD_DEVIATION 24.559 | 161.060 milligrams/deciliter (mg/dL) STANDARD_DEVIATION 1.372 | 138.527 milligrams/deciliter (mg/dL) STANDARD_DEVIATION 24.552 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 2 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 2 Participants | 11 Participants |
| Region of Enrollment United States | 11 Participants | 2 Participants | 13 Participants |
| Sex: Female, Male Female | 3 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 8 Participants | 2 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 11 | 1 / 2 |
| serious Total, serious adverse events | 0 / 11 | 0 / 2 |
Outcome results
Primary
Number of Participants With One or More Other Non-Serious Adverse Events (AEs) or Any Serious AEs (SAEs)
Events deemed to be SAEs by the Investigator as related to study drug administration were collected during the study and 30 days following study drug administration. A summary of SAEs and all other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module.
Time frame: Baseline through study completion (Day 127)
Population: All enrolled participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 1.0 mg/kg of LY3015014 | Number of Participants With One or More Other Non-Serious Adverse Events (AEs) or Any Serious AEs (SAEs) | AEs | 3 Participants |
| 1.0 mg/kg of LY3015014 | Number of Participants With One or More Other Non-Serious Adverse Events (AEs) or Any Serious AEs (SAEs) | SAEs | 0 Participants |
| Placebo | Number of Participants With One or More Other Non-Serious Adverse Events (AEs) or Any Serious AEs (SAEs) | AEs | 1 Participants |
| Placebo | Number of Participants With One or More Other Non-Serious Adverse Events (AEs) or Any Serious AEs (SAEs) | SAEs | 0 Participants |
Secondary
Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C)
Percentage change from baseline in LDL-C was calculated as Least Squares (LS) mean using mixed model repeated measures (MMRM) analysis adjusted for baseline measurement. Treatment, day after dosing, and treatment-by-day interaction were included in the model.
Time frame: Baseline, Day 43 and Day 57
Population: Pharmacodynamic analyses set: Participants who received at least 1 dose of investigational product according to the treatment actually received and had a baseline measurement and at least 1 post baseline measurement for LDL-C.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| 1.0 mg/kg of LY3015014 | Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | Day 43 | -49.10 µg/mL |
| 1.0 mg/kg of LY3015014 | Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | Day 57 | -37.53 µg/mL |
| Placebo | Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | Day 43 | 1.38 µg/mL |
| Placebo | Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) | Day 57 | 7.58 µg/mL |
p-value: <0.00190% CI: [-71.27, -29.7]Mixed Effects Model Analysis
p-value: <0.00190% CI: [-65.91, -24.31]Mixed Effects Models Analysis
Secondary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014
The Cmax was calculated after each dose of LY3015014.
Time frame: Day 1 and 29: 4 hours (h) and 24 h postdose
Population: Full analysis set (FAS): Data from all randomized participants who received at least 1 dose of the study drug according to the treatment the participants actually received and had evaluable PK data for Cmax.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.0 mg/kg of LY3015014 | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014 | After Day 1 dosing | 5.06 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 36 |
| 1.0 mg/kg of LY3015014 | Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY3015014 | After Day 29 dosing | 5.57 micrograms per milliliter (µg/mL) | Geometric Coefficient of Variation 58 |
Secondary
PK: Area Under the Concentration Curve During One Dosing Interval (AUCt) of LY3015014
The AUCt was calculated after each dose of LY3015014.
Time frame: Day 1 and 29: 4 h and 24 h postdose
Population: FAS: Data from all randomized participants who received at least 1 dose of study drug according to the treatment the participants actually received and had evaluable PK data for AUCt.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 1.0 mg/kg of LY3015014 | PK: Area Under the Concentration Curve During One Dosing Interval (AUCt) of LY3015014 | After Day 1 dosing | 1960 microgram*hour per milliliter (µg*h/mL) | Geometric Coefficient of Variation 37 |
| 1.0 mg/kg of LY3015014 | PK: Area Under the Concentration Curve During One Dosing Interval (AUCt) of LY3015014 | After Day 29 dosing | 2150 microgram*hour per milliliter (µg*h/mL) | Geometric Coefficient of Variation 46 |
Secondary
PK: Time of Maximum Concentration (Tmax) of LY3015014
tmax was calculated after each dosing of LY3015014 and is reported as the number of days for observed maximum concentration of LY3015014.
Time frame: Day 1 and 29: 4 h and 24 h postdose
Population: FAS: Data from all randomized participants who received at least 1 dose of study drug according to the treatment the participants actually received and had evaluable PK data for tmax.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 1.0 mg/kg of LY3015014 | PK: Time of Maximum Concentration (Tmax) of LY3015014 | After Day 1 dosing | 4 days |
| 1.0 mg/kg of LY3015014 | PK: Time of Maximum Concentration (Tmax) of LY3015014 | After Day 29 dosing | 5 days |