Dyslipidemia
Conditions
Keywords
abnormal cholesterol
Brief summary
The main purpose of this study is to measure how much of the drug gets into the blood stream and how long it takes the body to get rid of it when given once a day for 12, 24, and 52 weeks to participants with abnormal amounts of cholesterol and/or fat in the blood stream. Information about any side effects that may occur will also be collected. This study will also evaluate how the study drug reacts in the body when given once a day for 12, 24 and 52 weeks and how the body responds and returns to normal when the treatment is complete. The relationship between study drug and the results from the how the study drug reacts in the body may be explored, if needed.
Interventions
DRUGEvacetrapib
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Generally healthy participants or have stable medical conditions that, in the investigator's opinion, will not significantly alter the disposition of the drug, will not place the participant at increased risk by participating in the study, and will not interfere with interpretation of the data and meets one of the following criteria: * Elevated low-density lipoprotein cholesterol (LDL-C) greater than 100 milligrams per deciliter (mg/dL), OR * Low high-density lipoprotein cholesterol (HDL-C) less than 45 mg/dL (men); less than 50 mg/dL (women), OR * Hypercholesterolemia on stable statin therapy for at least 3 month * Have a body mass index (BMI) of 18 to 37 kilograms per square meter (kg/m\^2), inclusive, at screening
Exclusion criteria
* Have known allergies or intolerance to evacetrapib, related compounds * Have history of recurrent rashes or chronic skin conditions * Have significant history of or current chronic, active inflammatory conditions * Have history or current evidence of significant neurological disorder * Have long-standing diabetes that is insulin requiring * Have history of or current symptoms of malabsorption syndromes, history of gastric bypass surgery
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK) Parameters of Evacetrapib: Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC[0-tlast]) | Single-Dose: 1,2,3,4,6,8,12,24,36,48,72,120,168 Hours Postdose; Multiple Dose: Predose, 1,2,3,4,6,8,12,24,36,48,72,120,168 hours; 10,13,17,20,24,29,36,43,50,57, and 71 Days Post Dose |
| PK Parameters of Evacetrapib: Maximum Concentration (Cmax) | Single-Dose: 1,2,3,4,6,8,12,24,36,48,72,120,168 Hours Postdose; Multiple Dose: Predose, 1,2,3,4,6,8,12,24,36,48,72,120,168 hours; 10,13,17,20,24,29,36,43,50,57, and 71 Days Post Dose |
| PK Parameters of Evacetrapib: Terminal Half-life | Single-Dose: 1,2,3,4,6,8,12,24,36,48,72,120,168 Hours Postdose; Multiple Dose: Predose, 1,2,3,4,6,8,12,24,36,48,72,120,168 hours; 10,13,17,20,24,29,36,43,50,57, and 71 Days Post Dose |
Secondary
| Measure | Time frame |
|---|---|
| PD Parameters of Evacetrapib: High Density Lipoprotein Cholesterol (HDL-C) Level | Day -1, Day 8 |
| PD Parameters of Evacetrapib: Triglyceride Level | Day -1, Day 8 |
| PD Parameters of Evacetrapib: Low-Density Lipoprotein Cholesterol (LDL-C) Level | Day -1, Day 8 |
| PD Parameters of Evacetrapib: Total Cholesterol Level | Day -1, Day 8 |
Countries
United States
Participant flow
Pre-assignment details
Participants were enrolled into 3 parallel cohorts. Each participant received a single dose, after which PK was evaluated for 7 days, and then continued receiving once daily doses for 12, 24, or 52 weeks. After the last once-daily dose, PK was again evaluated in each participant until the concentration of evacetrapib was too low to be measurable.
Participants by arm
| Arm | Count |
|---|---|
| Evacetrapib: Multiple Dose 12 Weeks 130 mg of evacetrapib administered orally once daily beginning on Day 8 for 12 consecutive weeks | 30 |
| Evacetrapib: Multiple Dose 24 Weeks 130 mg of evacetrapib administered orally once daily beginning on Day 8 for 24 consecutive weeks | 32 |
| Evacetrapib: Multiple Dose 52 Weeks 130 mg of evacetrapib administered orally once daily beginning on Day 8 for 52 consecutive weeks | 39 |
| Total | 101 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 0 |
| Overall Study | Sponsor Decision | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Evacetrapib: Multiple Dose 52 Weeks | Total | Evacetrapib: Multiple Dose 12 Weeks | Evacetrapib: Multiple Dose 24 Weeks |
|---|---|---|---|---|
| Age, Continuous | 56.4 years STANDARD_DEVIATION 9.4 | 53.8 years STANDARD_DEVIATION 13 | 53.2 years STANDARD_DEVIATION 14.5 | 51.1 years STANDARD_DEVIATION 14.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 13 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants | 88 Participants | 25 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 3 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 27 Participants | 10 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 71 Participants | 20 Participants | 23 Participants |
| Region of Enrollment United States | 39 Participants | 101 Participants | 30 Participants | 32 Participants |
| Sex: Female, Male Female | 20 Participants | 55 Participants | 17 Participants | 18 Participants |
| Sex: Female, Male Male | 19 Participants | 46 Participants | 13 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 101 | 13 / 30 | 17 / 32 | 22 / 39 |
| serious Total, serious adverse events | 0 / 101 | 0 / 30 | 0 / 32 | 5 / 39 |
Outcome results
Primary
Pharmacokinetics (PK) Parameters of Evacetrapib: Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC[0-tlast])
Time frame: Single-Dose: 1,2,3,4,6,8,12,24,36,48,72,120,168 Hours Postdose; Multiple Dose: Predose, 1,2,3,4,6,8,12,24,36,48,72,120,168 hours; 10,13,17,20,24,29,36,43,50,57, and 71 Days Post Dose
Population: All enrolled participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Evacetrapib: Single Dose, All Participants | Pharmacokinetics (PK) Parameters of Evacetrapib: Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC[0-tlast]) | 14200 nanogram∙hour/mililliter (ng∙h/mL) | Geometric Coefficient of Variation 28 |
| Evacetrapib: Multiple Dose 12 Weeks | Pharmacokinetics (PK) Parameters of Evacetrapib: Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC[0-tlast]) | 37400 nanogram∙hour/mililliter (ng∙h/mL) | Geometric Coefficient of Variation 43 |
| Evacetrapib: Multiple Dose 24 Weeks | Pharmacokinetics (PK) Parameters of Evacetrapib: Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC[0-tlast]) | 36900 nanogram∙hour/mililliter (ng∙h/mL) | Geometric Coefficient of Variation 39 |
| Evacetrapib: Multiple Dose 52 Weeks | Pharmacokinetics (PK) Parameters of Evacetrapib: Area Under the Concentration Versus Time Curve From Time Zero to the Last Time Point With a Measurable Concentration (AUC[0-tlast]) | 44400 nanogram∙hour/mililliter (ng∙h/mL) | Geometric Coefficient of Variation 32 |
Primary
PK Parameters of Evacetrapib: Maximum Concentration (Cmax)
Time frame: Single-Dose: 1,2,3,4,6,8,12,24,36,48,72,120,168 Hours Postdose; Multiple Dose: Predose, 1,2,3,4,6,8,12,24,36,48,72,120,168 hours; 10,13,17,20,24,29,36,43,50,57, and 71 Days Post Dose
Population: All enrolled participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Evacetrapib: Single Dose, All Participants | PK Parameters of Evacetrapib: Maximum Concentration (Cmax) | 1020 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
| Evacetrapib: Multiple Dose 12 Weeks | PK Parameters of Evacetrapib: Maximum Concentration (Cmax) | 1690 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
| Evacetrapib: Multiple Dose 24 Weeks | PK Parameters of Evacetrapib: Maximum Concentration (Cmax) | 1770 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 39 |
| Evacetrapib: Multiple Dose 52 Weeks | PK Parameters of Evacetrapib: Maximum Concentration (Cmax) | 1850 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
Primary
PK Parameters of Evacetrapib: Terminal Half-life
Time frame: Single-Dose: 1,2,3,4,6,8,12,24,36,48,72,120,168 Hours Postdose; Multiple Dose: Predose, 1,2,3,4,6,8,12,24,36,48,72,120,168 hours; 10,13,17,20,24,29,36,43,50,57, and 71 Days Post Dose
Population: A single terminal half-life estimate was calculated from population PK estimates for apparent clearance and apparent volume of distribution across all participants, based on all available single dose data and multiple dose data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Evacetrapib: Single Dose, All Participants | PK Parameters of Evacetrapib: Terminal Half-life | 52.5 Days |
Secondary
PD Parameters of Evacetrapib: High Density Lipoprotein Cholesterol (HDL-C) Level
Time frame: Day -1, Day 8
Population: All enrolled participants in the single dose phase and had evaluable PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evacetrapib: Single Dose, All Participants | PD Parameters of Evacetrapib: High Density Lipoprotein Cholesterol (HDL-C) Level | Single-Dose Phase Day -1 | 1.538 millimole/Liter (mmol/L) | Standard Deviation 0.416 |
| Evacetrapib: Single Dose, All Participants | PD Parameters of Evacetrapib: High Density Lipoprotein Cholesterol (HDL-C) Level | Single-dose Phase Day 8 | 1.724 millimole/Liter (mmol/L) | Standard Deviation 0.493 |
| Evacetrapib: Multiple Dose 12 Weeks | PD Parameters of Evacetrapib: High Density Lipoprotein Cholesterol (HDL-C) Level | Single-Dose Phase Day -1 | 1.562 millimole/Liter (mmol/L) | Standard Deviation 0.395 |
| Evacetrapib: Multiple Dose 12 Weeks | PD Parameters of Evacetrapib: High Density Lipoprotein Cholesterol (HDL-C) Level | Single-dose Phase Day 8 | 1.777 millimole/Liter (mmol/L) | Standard Deviation 0.443 |
| Evacetrapib: Multiple Dose 24 Weeks | PD Parameters of Evacetrapib: High Density Lipoprotein Cholesterol (HDL-C) Level | Single-Dose Phase Day -1 | 1.670 millimole/Liter (mmol/L) | Standard Deviation 0.548 |
| Evacetrapib: Multiple Dose 24 Weeks | PD Parameters of Evacetrapib: High Density Lipoprotein Cholesterol (HDL-C) Level | Single-dose Phase Day 8 | 1.772 millimole/Liter (mmol/L) | Standard Deviation 0.552 |
Secondary
PD Parameters of Evacetrapib: Low-Density Lipoprotein Cholesterol (LDL-C) Level
Time frame: Day -1, Day 8
Population: All enrolled participants who received at least 1 dose of study drug and had evaluable PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evacetrapib: Single Dose, All Participants | PD Parameters of Evacetrapib: Low-Density Lipoprotein Cholesterol (LDL-C) Level | Single-Dose Phase Day -1 | 3.711 mmol/L | Standard Deviation 0.958 |
| Evacetrapib: Single Dose, All Participants | PD Parameters of Evacetrapib: Low-Density Lipoprotein Cholesterol (LDL-C) Level | Single-Dose Phase Day 8 | 3.173 mmol/L | Standard Deviation 0.872 |
| Evacetrapib: Multiple Dose 12 Weeks | PD Parameters of Evacetrapib: Low-Density Lipoprotein Cholesterol (LDL-C) Level | Single-Dose Phase Day -1 | 3.359 mmol/L | Standard Deviation 0.835 |
| Evacetrapib: Multiple Dose 12 Weeks | PD Parameters of Evacetrapib: Low-Density Lipoprotein Cholesterol (LDL-C) Level | Single-Dose Phase Day 8 | 3.152 mmol/L | Standard Deviation 0.928 |
| Evacetrapib: Multiple Dose 24 Weeks | PD Parameters of Evacetrapib: Low-Density Lipoprotein Cholesterol (LDL-C) Level | Single-Dose Phase Day -1 | 3.662 mmol/L | Standard Deviation 1.039 |
| Evacetrapib: Multiple Dose 24 Weeks | PD Parameters of Evacetrapib: Low-Density Lipoprotein Cholesterol (LDL-C) Level | Single-Dose Phase Day 8 | 3.293 mmol/L | Standard Deviation 1.058 |
Secondary
PD Parameters of Evacetrapib: Total Cholesterol Level
Time frame: Day -1, Day 8
Population: All enrolled participants who received at least 1 dose of study drug and had evaluable PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evacetrapib: Single Dose, All Participants | PD Parameters of Evacetrapib: Total Cholesterol Level | Single-Dose Phase Day 8 | 5.577 mmol | Standard Deviation 1.224 |
| Evacetrapib: Single Dose, All Participants | PD Parameters of Evacetrapib: Total Cholesterol Level | Single-Dose Phase Day -1 | 5.922 mmol | Standard Deviation 1.244 |
| Evacetrapib: Multiple Dose 12 Weeks | PD Parameters of Evacetrapib: Total Cholesterol Level | Single-Dose Phase Day 8 | 5.531 mmol | Standard Deviation 0.931 |
| Evacetrapib: Multiple Dose 12 Weeks | PD Parameters of Evacetrapib: Total Cholesterol Level | Single-Dose Phase Day -1 | 5.523 mmol | Standard Deviation 0.736 |
| Evacetrapib: Multiple Dose 24 Weeks | PD Parameters of Evacetrapib: Total Cholesterol Level | Single-Dose Phase Day 8 | 5.715 mmol | Standard Deviation 1.179 |
| Evacetrapib: Multiple Dose 24 Weeks | PD Parameters of Evacetrapib: Total Cholesterol Level | Single-Dose Phase Day -1 | 6.015 mmol | Standard Deviation 1.099 |
Secondary
PD Parameters of Evacetrapib: Triglyceride Level
Time frame: Day -1, Day 8
Population: All enrolled participants who received at least 1 dose of study drug and had evaluable PD data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evacetrapib: Single Dose, All Participants | PD Parameters of Evacetrapib: Triglyceride Level | Single-Dose Phase Day -1 | 1.474 mmol | Standard Deviation 0.849 |
| Evacetrapib: Single Dose, All Participants | PD Parameters of Evacetrapib: Triglyceride Level | Single-Dose Phase Day 8 | 1.482 mmol | Standard Deviation 1.016 |
| Evacetrapib: Multiple Dose 12 Weeks | PD Parameters of Evacetrapib: Triglyceride Level | Single-Dose Phase Day -1 | 1.311 mmol | Standard Deviation 0.815 |
| Evacetrapib: Multiple Dose 12 Weeks | PD Parameters of Evacetrapib: Triglyceride Level | Single-Dose Phase Day 8 | 1.309 mmol | Standard Deviation 0.871 |
| Evacetrapib: Multiple Dose 24 Weeks | PD Parameters of Evacetrapib: Triglyceride Level | Single-Dose Phase Day -1 | 1.485 mmol | Standard Deviation 0.631 |
| Evacetrapib: Multiple Dose 24 Weeks | PD Parameters of Evacetrapib: Triglyceride Level | Single-Dose Phase Day 8 | 1.419 mmol | Standard Deviation 0.681 |