Healthy Volunteers
Conditions
Brief summary
The main purpose of this study is to investigate how the body responds to evacetrapib and to evaluate the safety and the effect of evacetrapib, alone and in combination with selected statins, in healthy Chinese participants. The study has 2 parts. Part one will last up to 4 weeks and part two will last up to 5 weeks, not including screening. Participants may only enroll in one part.
Interventions
DRUGEvacetrapib
Administered orally.
DRUGSimvastatin
Administered orally.
DRUGAtorvastatin
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 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Are native Chinese and living in China. * Are overtly healthy males or females as determined by medical history and physical examination. * Female participants: * Women not of child-bearing potential * Women of child-bearing potential must correctly use 2 forms of reliable contraception to avoid getting pregnant during the study and for 3 months after the study is completed. * Body Mass Index: 19.0 to 24.0 kilogram per square meter (kg/m\^2) * BP and pulse rate at both supine and standing positions of approximately a systolic BP ≤ 140 millimeter of mercury (mm Hg), and diastolic BP ≤ 90 mm Hg * Participants with untreated hypercholesterolemia may be included if not on an herbal or other traditional Chinese medicines (TCM) * Have no known liver disease * Have given written informed consent
Exclusion criteria
* Are currently enrolled in a clinical trial involving an investigational product (IP) or off-label use of a drug or device, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. * Have known allergies to evacetrapib, simvastatin, or atorvastatin, related compounds or any components of the formulation * Have previously completed or withdrawn from this study or any other study investigating evacetrapib, and have previously received the IP within 3 months. * Have a history within the last year or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematologic, or neurologic 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. * Show evidence of significant active neuropsychiatric disease. * Regularly use known drugs of abuse * Are women with a positive pregnancy test or women who are lactating. * Have used or intend to use over-the-counter or prescription medications (including vitamins/mineral supplements) or TCM 14 days prior to the first dose and during the study. * Hormonal contraceptives are permitted. * Use of any drugs or substances that are known to be substrates, inducers, or inhibitors of organic anion transporting polypeptide 1B1 (OATP1B1), or of any other transporters involved in simvastatin or atorvastatin disposition, or of any drugs or substances that are known to be strong inducers or inhibitors of cytochrome P450 3A (CYP3A) within 30 days prior to the first dose and throughout the study. * Donated blood of \>400 mL within the last month. * Drink alcoholic beverages with intake that exceeds 28 units per week (males) and 21 units per week (females), or are unwilling to stop alcohol consumption 48 hours prior to dosing until discharge from the clinical research unit (CRU) (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits). * Are unwilling to comply with the dietary requirements/restrictions during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK: Time to Maximum Concentration (Tmax) of Evacetrapib | Part 1: Day 1 Predose on Day 1 or Day 14 and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, and 168 hours postdose. Part 2: Predose on Day 14 at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose. | Pharmacokinetic parameter estimates of evacetrapib following single and daily doses of 130 mg evacetrapib. |
| Pharmacokinetics (PK): Area Under Curve (AUC 0-inf) of Evacetrapib | Part 1: Day 1 Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, and 168 hours Postdose; Part 2 Day 14 Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24 hours Postdose | Pharmacokinetic (PK) parameter estimates from evacetrapib concentrations following single dose and daily dose of 130 mg evacetrapib. |
| PK: Maximum Concentration (Cmax) of Evacetrapib | Part 1: Day 1 and Day 14 Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, and 168 hours Postdose; Part 2 Day 14: Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours Postdose | Pharmacokinetic parameter estimates from evacetrapib following single dose and daily doses of 130 mg. |
| PK: Tmax of Evacetrapib Alone and With Simvastatin or Atorvastatin | Part 2: Predose on Day 14 and 22 and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose. | Pharmacokinetic parameter estimates of Tmax of evacetrapib following 130 mg daily dose alone or with 40 mg Simvastatin or 20 mg Atorvastatin. Tmax of simvastatin and atorvastatin. |
| PK: AUC of Evacetrapib Alone and With Simvastatin or Atorvastatin | Part 2: Day 14 and 22 Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours Postdose | Pharmacokinetic parameter estimates of evacetrapib following 130 mg evacetrapib daily alone or with 40 mg simvastatin or 20 mg atorvastatin daily AUC (0-24). |
| PK: Cmax of Evacetrapib Alone and With Simvastatin or Atorvastatin | Part 2: Day 14 and 22 Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours Postdose. | Pharmacokinetic parameter estimates of evacetrapib following 130 mg evacetrapib daily alone or with 40 mg simvastatin or 20 mg atorvastatin daily. |
Secondary
| Measure | Time frame |
|---|---|
| Effect of Evacetrapib Single and Multiple Doses on High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), and Triglycerides (TG) | Single Dose Day 2 and Multiple Dose Day 22 |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A Part 1, Cohort A, Period 1, Participants will receive a single oral 130 mg dose of evacetrapib.
Part 1, Cohort A, Period 2, Participants will receive multiple doses of evacetrapib 130 mg for 14 days. | 16 |
| Cohort B Part 2, Cohorts B, Period 1, Participants will receive simvastatin 40 mg orally, once daily on Days 1 - 4.
Part 2, Cohorts B, Period 2, Participants will receive a single oral 130 mg dose of evacetrapib on Days 5-14
Part 2, Cohorts B, Period 3, Participants will receive evacetrapib 130 mg and simvastatin 40mg orally, once daily on Days 15 - 22. | 24 |
| Cohort C Part 2, Cohorts C, Period 1, Participants will receive atorvastatin orally, once daily on Days 1 - 4.
Part 2, Cohorts C, Period 2, Participants will receive a single oral 130 mg dose of evacetrapib on Days 5-14
Part 2, Cohorts C, Period 3, Participants will receive evacetrapib 130 mg orally and atorvastatin 20 mg orally, once daily on Days 15 - 22. | 22 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period 1 | No Reason Given | 0 | 1 | 0 |
| Period 3 | Adverse Event | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort C | Cohort B | Cohort A |
|---|---|---|---|---|
| Age, Continuous | 28.02 years STANDARD_DEVIATION 5.25 | 27.9 years STANDARD_DEVIATION 4.9 | 27.5 years STANDARD_DEVIATION 2.9 | 29.1 years STANDARD_DEVIATION 8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 62 Participants | 22 Participants | 24 Participants | 16 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 62 Participants | 22 Participants | 24 Participants | 16 Participants |
| Sex: Female, Male Female | 5 Participants | 2 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 57 Participants | 20 Participants | 24 Participants | 13 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 | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 16 | 0 / 16 | 0 / 24 | 0 / 23 | 0 / 23 | 0 / 22 | 0 / 22 | 0 / 22 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 | 0 / 24 | 0 / 23 | 0 / 23 | 0 / 22 | 0 / 22 | 0 / 22 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under Curve (AUC 0-inf) of Evacetrapib
Pharmacokinetic (PK) parameter estimates from evacetrapib concentrations following single dose and daily dose of 130 mg evacetrapib.
Time frame: Part 1: Day 1 Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, and 168 hours Postdose; Part 2 Day 14 Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24 hours Postdose
Population: All participants who received at least one dose of study drug in Cohort A.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Evacetrapib Single and Multiple Dose | Pharmacokinetics (PK): Area Under Curve (AUC 0-inf) of Evacetrapib | Day 1 | 7700 nanogram * hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 74 |
| Evacetrapib Single and Multiple Dose | Pharmacokinetics (PK): Area Under Curve (AUC 0-inf) of Evacetrapib | Day 14 | 23600 nanogram * hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 33 |
Primary
PK: AUC of Evacetrapib Alone and With Simvastatin or Atorvastatin
Pharmacokinetic parameter estimates of evacetrapib following 130 mg evacetrapib daily alone or with 40 mg simvastatin or 20 mg atorvastatin daily AUC (0-24).
Time frame: Part 2: Day 14 and 22 Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours Postdose
Population: All participants who received at least one dose of study drug in Cohort B and C and had evaluable PK data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Evacetrapib Single and Multiple Dose | PK: AUC of Evacetrapib Alone and With Simvastatin or Atorvastatin | Days 5-14 | 10700 ng*h/mL | Geometric Coefficient of Variation 36 |
| Evacetrapib Single and Multiple Dose | PK: AUC of Evacetrapib Alone and With Simvastatin or Atorvastatin | Days 15-22 | 9640 ng*h/mL | Geometric Coefficient of Variation 48 |
| Evacetrapib Daily and Atorvastatin | PK: AUC of Evacetrapib Alone and With Simvastatin or Atorvastatin | Days 5-14 | 10600 ng*h/mL | Geometric Coefficient of Variation 30 |
| Evacetrapib Daily and Atorvastatin | PK: AUC of Evacetrapib Alone and With Simvastatin or Atorvastatin | Days 15-22 | 9480 ng*h/mL | Geometric Coefficient of Variation 53 |
Primary
PK: Cmax of Evacetrapib Alone and With Simvastatin or Atorvastatin
Pharmacokinetic parameter estimates of evacetrapib following 130 mg evacetrapib daily alone or with 40 mg simvastatin or 20 mg atorvastatin daily.
Time frame: Part 2: Day 14 and 22 Predose, 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours Postdose.
Population: All participants who received at least one dose of study drug in Cohort B and C and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Evacetrapib Single and Multiple Dose | PK: Cmax of Evacetrapib Alone and With Simvastatin or Atorvastatin | Days 5-14 | 1180 ng/mL | Geometric Coefficient of Variation 52 |
| Evacetrapib Single and Multiple Dose | PK: Cmax of Evacetrapib Alone and With Simvastatin or Atorvastatin | Days 15- 22 | 1020 ng/mL | Geometric Coefficient of Variation 68 |
| Evacetrapib Daily and Atorvastatin | PK: Cmax of Evacetrapib Alone and With Simvastatin or Atorvastatin | Days 5-14 | 1120 ng/mL | Geometric Coefficient of Variation 36 |
| Evacetrapib Daily and Atorvastatin | PK: Cmax of Evacetrapib Alone and With Simvastatin or Atorvastatin | Days 15- 22 | 1000 ng/mL | Geometric Coefficient of Variation 73 |
Primary
PK: Maximum Concentration (Cmax) of Evacetrapib
Pharmacokinetic parameter estimates from evacetrapib following single dose and daily doses of 130 mg.
Time frame: Part 1: Day 1 and Day 14 Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, and 168 hours Postdose; Part 2 Day 14: Predose 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours Postdose
Population: All participants who received at least one dose of study drug in Cohort A.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Evacetrapib Single and Multiple Dose | PK: Maximum Concentration (Cmax) of Evacetrapib | Single Dose Day 1 | 418 ng/mL | Geometric Coefficient of Variation 118 |
| Evacetrapib Single and Multiple Dose | PK: Maximum Concentration (Cmax) of Evacetrapib | Multiple Dose Day 14 | 954 ng/mL | Geometric Coefficient of Variation 52 |
Primary
PK: Time to Maximum Concentration (Tmax) of Evacetrapib
Pharmacokinetic parameter estimates of evacetrapib following single and daily doses of 130 mg evacetrapib.
Time frame: Part 1: Day 1 Predose on Day 1 or Day 14 and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, and 168 hours postdose. Part 2: Predose on Day 14 at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post dose.
Population: All participants who received at least one dose of study drug in Cohort A.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Evacetrapib Single and Multiple Dose | PK: Time to Maximum Concentration (Tmax) of Evacetrapib | Single Dose Day 1 | 3.00 hours (h) |
| Evacetrapib Single and Multiple Dose | PK: Time to Maximum Concentration (Tmax) of Evacetrapib | Daily Dose Day 14 | 3.00 hours (h) |
Primary
PK: Tmax of Evacetrapib Alone and With Simvastatin or Atorvastatin
Pharmacokinetic parameter estimates of Tmax of evacetrapib following 130 mg daily dose alone or with 40 mg Simvastatin or 20 mg Atorvastatin. Tmax of simvastatin and atorvastatin.
Time frame: Part 2: Predose on Day 14 and 22 and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 hours postdose.
Population: All participants who received at least one dose of study drug in Cohort B and C and had evaluable PK data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Evacetrapib Single and Multiple Dose | PK: Tmax of Evacetrapib Alone and With Simvastatin or Atorvastatin | Days 5-14 | 3.00 h |
| Evacetrapib Single and Multiple Dose | PK: Tmax of Evacetrapib Alone and With Simvastatin or Atorvastatin | Days 15- 22 | 3.00 h |
| Evacetrapib Daily and Atorvastatin | PK: Tmax of Evacetrapib Alone and With Simvastatin or Atorvastatin | Days 5-14 | 3.00 h |
| Evacetrapib Daily and Atorvastatin | PK: Tmax of Evacetrapib Alone and With Simvastatin or Atorvastatin | Days 15- 22 | 3.00 h |
Secondary
Effect of Evacetrapib Single and Multiple Doses on High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), and Triglycerides (TG)
Time frame: Single Dose Day 2 and Multiple Dose Day 22
Population: All participants who received at least one dose of study drug in Cohort A.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Evacetrapib Single and Multiple Dose | Effect of Evacetrapib Single and Multiple Doses on High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), and Triglycerides (TG) | HDL-C | 1.641 millimoles per liter (mmol/L) | Standard Deviation 0.211 |
| Evacetrapib Single and Multiple Dose | Effect of Evacetrapib Single and Multiple Doses on High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), and Triglycerides (TG) | LDL-C | 2.289 millimoles per liter (mmol/L) | Standard Deviation 0.483 |
| Evacetrapib Single and Multiple Dose | Effect of Evacetrapib Single and Multiple Doses on High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), and Triglycerides (TG) | TG | 0.984 millimoles per liter (mmol/L) | Standard Deviation 0.312 |
| Evacetrapib Daily and Atorvastatin | Effect of Evacetrapib Single and Multiple Doses on High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), and Triglycerides (TG) | HDL-C | 2.676 millimoles per liter (mmol/L) | Standard Deviation 0.373 |
| Evacetrapib Daily and Atorvastatin | Effect of Evacetrapib Single and Multiple Doses on High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), and Triglycerides (TG) | LDL-C | 1.241 millimoles per liter (mmol/L) | Standard Deviation 0.574 |
| Evacetrapib Daily and Atorvastatin | Effect of Evacetrapib Single and Multiple Doses on High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), and Triglycerides (TG) | TG | 1.221 millimoles per liter (mmol/L) | Standard Deviation 0.356 |