Healthy Volunteers
Conditions
Brief summary
The purpose of this study is to determine whether concentrations of the study drug (evacetrapib) in the blood stream is the same or is different when the person is also taking gemfibrozil (a drug used to lower lipid levels). Each participant will receive gemfibrozil alone, evacetrapib alone, and both drugs in combination. There is no washout period between doses. The safety of both of the study drugs given together will be evaluated. Information about any side effects that may have occurred will also be collected. This study will last approximately 36 days.
Interventions
DRUGEvacetrapib
DRUGGemfibrozil
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy participants as determined by medical history and physical examination * Have a body mass index of 18 to 32 kilograms per square meter (kg/m\^2)
Exclusion criteria
* Have known allergies to evacetrapib and gemfibrozil, related compounds or any components of the formulation * Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study * Regularly use known drugs of abuse and/or show positive findings on urinary drug screening * Currently smoke cigarettes or use tobacco or nicotine substitutes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Evacetrapib | Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Day 11 and Day 22 | Venous blood samples were taken on Day 11 for PK parameter estimates of evacetrapib alone and on Day 22 for PK parameter estimates of evacetrapib when coadministered with gemfibrozil. |
| Pharmacokinetics (PK): Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Evacetrapib | Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Day 11 and Day 22 | Venous blood samples were taken on Day 11 for PK parameter estimates of evacetrapib alone and on Day 22 for PK parameter estimates of evacetrapib when coadministered with gemfibrozil. |
| Pharmacokinetics (PK): Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib | Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Day 11 and Day 22 | Venous blood samples were taken on Day 11 for PK parameter estimates of evacetrapib alone and on Day 22 for PK parameter estimates of evacetrapib when coadministered with gemfibrozil. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Curve Over a 12 Hour Dosing Interval (AUCτ) of Gemfibrozil | Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and Day 13 | Venous blood samples were taken on Day 1 for PK parameter estimates of gemfibrozil alone and on Day 13 for PK parameter estimates of gemfibrozil when coadministered with evacetrapib. |
| Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Gemfibrozil | Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and Day 13 | Venous blood samples were taken on Day 1 for PK parameter estimates of gemfibrozil alone and on Day 13 for PK parameter estimates of gemfibrozil when coadministered with evacetrapib. |
| Pharmacokinetics (PK): Time of Maximum Observed Drug Concentration (Tmax) of Gemfibrozil | Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and Day 13 | Venous blood samples were taken on Day 1 for PK parameter estimates of gemfibrozil alone and on Day 13 for PK parameter estimates of gemfibrozil when coadministered with evacetrapib. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants were assigned to the following treatment regimen:
Period 1: Single oral dose of 600 mg gemfibrozil in the morning of Day 1.
Period 2: Oral doses of 130 mg evacetrapib QD for 11 days (Days 2 to 12).
Period 3: Oral doses of 600 mg gemfibrozil BID and 130 mg evacetrapib QD for 10 days (Days 13 to 22), with a single dose of 600 mg gemfibrozil on Day 23. | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 2 (Days 2 to 12) | Adverse Event | 3 |
| Period 3 (Days 13 to 23) | Adverse Event | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 41.8 years STANDARD_DEVIATION 10.4 |
| Race/Ethnicity, Customized Black | 7 Participants |
| Race/Ethnicity, Customized Multiple | 3 Participants |
| Race/Ethnicity, Customized White | 14 Participants |
| Region of Enrollment United States | 24 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 24 | 8 / 24 | 7 / 21 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 21 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Evacetrapib
Venous blood samples were taken on Day 11 for PK parameter estimates of evacetrapib alone and on Day 22 for PK parameter estimates of evacetrapib when coadministered with gemfibrozil.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Day 11 and Day 22
Population: All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable AUCτ data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Evacetrapib | Pharmacokinetics (PK): Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Evacetrapib | 11300 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 20 |
| Evacetrapib + Gemfibrozil | Pharmacokinetics (PK): Area Under the Concentration Curve Over a 24 Hour Dosing Interval (AUCτ) of Evacetrapib | 11400 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 21 |
Primary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Evacetrapib
Venous blood samples were taken on Day 11 for PK parameter estimates of evacetrapib alone and on Day 22 for PK parameter estimates of evacetrapib when coadministered with gemfibrozil.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Day 11 and Day 22
Population: All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Evacetrapib | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Evacetrapib | 1270 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 26 |
| Evacetrapib + Gemfibrozil | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Evacetrapib | 1290 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 26 |
Primary
Pharmacokinetics (PK): Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib
Venous blood samples were taken on Day 11 for PK parameter estimates of evacetrapib alone and on Day 22 for PK parameter estimates of evacetrapib when coadministered with gemfibrozil.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose on Day 11 and Day 22
Population: All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable Tmax data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Evacetrapib | Pharmacokinetics (PK): Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib | 4.00 hours |
| Evacetrapib + Gemfibrozil | Pharmacokinetics (PK): Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib | 3.00 hours |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Curve Over a 12 Hour Dosing Interval (AUCτ) of Gemfibrozil
Venous blood samples were taken on Day 1 for PK parameter estimates of gemfibrozil alone and on Day 13 for PK parameter estimates of gemfibrozil when coadministered with evacetrapib.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and Day 13
Population: All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable AUCτ data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Evacetrapib | Pharmacokinetics (PK): Area Under the Concentration Curve Over a 12 Hour Dosing Interval (AUCτ) of Gemfibrozil | 55700 ng*h/mL | Geometric Coefficient of Variation 23 |
| Evacetrapib + Gemfibrozil | Pharmacokinetics (PK): Area Under the Concentration Curve Over a 12 Hour Dosing Interval (AUCτ) of Gemfibrozil | 53800 ng*h/mL | Geometric Coefficient of Variation 22 |
Secondary
Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Gemfibrozil
Venous blood samples were taken on Day 1 for PK parameter estimates of gemfibrozil alone and on Day 13 for PK parameter estimates of gemfibrozil when coadministered with evacetrapib.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and Day 13
Population: All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Evacetrapib | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Gemfibrozil | 17400 ng/mL | Geometric Coefficient of Variation 32 |
| Evacetrapib + Gemfibrozil | Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) of Gemfibrozil | 16800 ng/mL | Geometric Coefficient of Variation 34 |
Secondary
Pharmacokinetics (PK): Time of Maximum Observed Drug Concentration (Tmax) of Gemfibrozil
Venous blood samples were taken on Day 1 for PK parameter estimates of gemfibrozil alone and on Day 13 for PK parameter estimates of gemfibrozil when coadministered with evacetrapib.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours postdose on Day 1 and Day 13
Population: All participants who received at least 1 dose of evacetrapib or gemfibrozil and had evaluable Tmax data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Evacetrapib | Pharmacokinetics (PK): Time of Maximum Observed Drug Concentration (Tmax) of Gemfibrozil | 1.00 hours |
| Evacetrapib + Gemfibrozil | Pharmacokinetics (PK): Time of Maximum Observed Drug Concentration (Tmax) of Gemfibrozil | 1.08 hours |