Hepatic Insufficiency
Conditions
Brief summary
The purpose of this study is to measure how much of the drug gets into the bloodstream and how long it takes the body to remove it when given to participants with hepatic (liver) impairment compared to participants with normal hepatic function. Information about any side effects that may occur will also be collected. This study will last approximately 28 days, not including screening.
Interventions
DRUGEvacetrapib
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Participants have given written informed consent approved by the ethical review board (ERB) governing the site * Female participants should be of non-childbearing potential * Have a body mass index (BMI) of 18 to 40 kilograms per square meter (kg/m\^2) * Healthy participants have normal hepatic function as determined by medical history, physical examination, and other screening procedures * Individuals with hepatic impairment classified as Child-Pugh score A, B, or C (mild, moderate, or severe impairment)
Exclusion criteria
* Has had esophagus variceal bleeding within 3 months of check-in * Have the need to take medications that may interfere with how the liver removes the drug * Have evidence of cancer in the liver * Consumes excessively large amounts of drinks with caffeine or alcohol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Time Tlast (AUC0-tlast) of Evacetrapib | Predose on Day 1, and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours after the Day 1 dose | tlast is defined as the last time point with a measurable concentration of Evacetrapib. |
| PK: Maximum Observed Concentration (Cmax) of Evacetrapib | Predose on Day 1, and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours after the Day 1 dose | — |
| PK: Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib | Predose on Day 1, and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours after the Day 1 dose | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Evacetrapib (Healthy) Group 1: 130 milligrams (mg) evacetrapib administered once, orally as a tablet to participants with normal hepatic function | 10 |
| Evacetrapib (Hepatic, Mild) Group 2: 130 mg evacetrapib administered once, orally as a tablet to participants with mild hepatic impairment | 8 |
| Evacetrapib (Hepatic, Moderate) Group 3: 130 mg evacetrapib administered once, orally as a tablet to participants with moderate hepatic impairment | 8 |
| Evacetrapib (Hepatic, Severe) Group 4: 130 mg evacetrapib administered once, orally as a tablet to participants with severe hepatic impairment | 6 |
| Total | 32 |
Baseline characteristics
| Characteristic | Evacetrapib (Healthy) | Total | Evacetrapib (Hepatic, Severe) | Evacetrapib (Hepatic, Moderate) | Evacetrapib (Hepatic, Mild) |
|---|---|---|---|---|---|
| Age, Continuous | 54.4 years STANDARD_DEVIATION 8.6 | 56.0 years STANDARD_DEVIATION 7.2 | 57.8 years STANDARD_DEVIATION 4.7 | 58.6 years STANDARD_DEVIATION 9.6 | 54.1 years STANDARD_DEVIATION 2.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 17 Participants | 3 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 15 Participants | 3 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 29 Participants | 6 Participants | 8 Participants | 6 Participants |
| Region of Enrollment United States | 10 Participants | 32 Participants | 6 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Female | 4 Participants | 11 Participants | 1 Participants | 2 Participants | 4 Participants |
| Sex: Female, Male Male | 6 Participants | 21 Participants | 5 Participants | 6 Participants | 4 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 | 2 / 10 | 4 / 8 | 3 / 8 | 3 / 6 |
| serious Total, serious adverse events | 0 / 10 | 0 / 8 | 0 / 8 | 0 / 6 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Time Tlast (AUC0-tlast) of Evacetrapib
tlast is defined as the last time point with a measurable concentration of Evacetrapib.
Time frame: Predose on Day 1, and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours after the Day 1 dose
Population: Participants who received at least 1 dose of study drug and had evaluable PK (AUC0-tlast) data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Evacetrapib (Healthy) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Time Tlast (AUC0-tlast) of Evacetrapib | 10700 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 50 |
| Evacetrapib (Hepatic, Mild) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Time Tlast (AUC0-tlast) of Evacetrapib | 10500 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 84 |
| Evacetrapib (Hepatic, Moderate) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Time Tlast (AUC0-tlast) of Evacetrapib | 13200 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 49 |
| Evacetrapib (Hepatic, Severe) | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Time Tlast (AUC0-tlast) of Evacetrapib | 15800 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 62 |
Primary
PK: Maximum Observed Concentration (Cmax) of Evacetrapib
Time frame: Predose on Day 1, and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours after the Day 1 dose
Population: Participants who received at least 1 dose of study drug and had evaluable PK (Cmax) data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Evacetrapib (Healthy) | PK: Maximum Observed Concentration (Cmax) of Evacetrapib | 605 ng/mL | Geometric Coefficient of Variation 98 |
| Evacetrapib (Hepatic, Mild) | PK: Maximum Observed Concentration (Cmax) of Evacetrapib | 609 ng/mL | Geometric Coefficient of Variation 144 |
| Evacetrapib (Hepatic, Moderate) | PK: Maximum Observed Concentration (Cmax) of Evacetrapib | 591 ng/mL | Geometric Coefficient of Variation 58 |
| Evacetrapib (Hepatic, Severe) | PK: Maximum Observed Concentration (Cmax) of Evacetrapib | 478 ng/mL | Geometric Coefficient of Variation 51 |
Primary
PK: Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib
Time frame: Predose on Day 1, and 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 72, 120, 168, 216, 264, 312, and 336 hours after the Day 1 dose
Population: Participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Evacetrapib (Healthy) | PK: Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib | 3 h |
| Evacetrapib (Hepatic, Mild) | PK: Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib | 3 h |
| Evacetrapib (Hepatic, Moderate) | PK: Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib | 3 h |
| Evacetrapib (Hepatic, Severe) | PK: Time of Maximum Observed Drug Concentration (Tmax) of Evacetrapib | 3 h |