Hepatic Insufficiency
Conditions
Brief summary
The study involves a single dose of a study drug called abemaciclib taken by mouth. The purpose of this study will be to measure how much study drug gets into the blood stream and how long the body takes to get rid of it when given to participants with mild, moderate, or severe liver impairment compared to healthy participants. In addition, the tolerability of the study drug will be evaluated. This study will last approximately 3 weeks for each participant, including check-in and follow-up.
Interventions
DRUGAbemaciclib
Administered Orally
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 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Female participants must be of non-child-bearing potential * Have a body mass index of 18 to 40 kilograms per square meter (kg/m²)
Exclusion criteria
* No history of cardiovascular, renal, respiratory, gastrointestinal, endocrine or hematological disorders * Have known allergies to abemaciclib, related compounds, or any components of the formulation * No human immunodeficiency virus (HIV) infection or antibodies
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | Day 1: Predose, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, and 192 Hours Postdose |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | Day 1: Predose, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, and 192 Hours Postdose |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Abemaciclib: Normal Hepatic Function 200 mg abemaciclib administered once, orally, to participants with normal hepatic function. | 10 |
| Abemaciclib: Mild Hepatic Impairment 200 mg abemaciclib administered once, orally, to participants with mild hepatic impairment. | 9 |
| Abemaciclib: Moderate Hepatic Impairment 200 mg abemaciclib administered once, orally, to participants with moderate hepatic impairment. | 10 |
| Abemaciclib: Severe Hepatic Impairment 200 mg abemaciclib administered once, orally, to participants with severe hepatic impairment. | 6 |
| Total | 35 |
Baseline characteristics
| Characteristic | Abemaciclib: Normal Hepatic Function | Total | Abemaciclib: Severe Hepatic Impairment | Abemaciclib: Moderate Hepatic Impairment | Abemaciclib: Mild Hepatic Impairment |
|---|---|---|---|---|---|
| Age, Continuous | 55.0 years STANDARD_DEVIATION 4.8 | 56.2 years STANDARD_DEVIATION 5.3 | 53.2 years STANDARD_DEVIATION 6.2 | 58.8 years STANDARD_DEVIATION 5.5 | 56.6 years STANDARD_DEVIATION 4.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 8 Participants | 4 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 27 Participants | 2 Participants | 10 Participants | 7 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 | 1 Participants | 1 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 | 3 Participants | 7 Participants | 0 Participants | 3 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 | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 25 Participants | 4 Participants | 7 Participants | 7 Participants |
| Region of Enrollment United States | 10 Participants | 35 Participants | 6 Participants | 10 Participants | 9 Participants |
| Sex: Female, Male Female | 5 Participants | 13 Participants | 2 Participants | 3 Participants | 3 Participants |
| Sex: Female, Male Male | 5 Participants | 22 Participants | 4 Participants | 7 Participants | 6 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 | 4 / 10 | 6 / 9 | 7 / 10 | 3 / 6 |
| serious Total, serious adverse events | 0 / 10 | 0 / 9 | 1 / 10 | 0 / 6 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites
Time frame: Day 1: Predose, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, and 192 Hours Postdose
Population: All participants who received abemaciclib and had evaluable plasma values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Abemaciclib: Normal Hepatic Function | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | LSN3106726 | 3120 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 40 |
| Abemaciclib: Normal Hepatic Function | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | LSN2839567 | 1420 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 40 |
| Abemaciclib: Normal Hepatic Function | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | LSN3106729 | 480 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 55 |
| Abemaciclib: Normal Hepatic Function | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | Abemaciclib | 4460 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 61 |
| Abemaciclib: Mild Hepatic Impairment | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | LSN2839567 | 1090 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 34 |
| Abemaciclib: Mild Hepatic Impairment | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | Abemaciclib | 4280 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 58 |
| Abemaciclib: Mild Hepatic Impairment | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | LSN3106726 | 2200 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 39 |
| Abemaciclib: Mild Hepatic Impairment | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | LSN3106729 | 257 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 42 |
| Abemaciclib: Moderate Hepatic Impairment | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | Abemaciclib | 4940 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 51 |
| Abemaciclib: Moderate Hepatic Impairment | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | LSN2839567 | 921 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 46 |
| Abemaciclib: Moderate Hepatic Impairment | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | LSN3106726 | 1570 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 57 |
| Abemaciclib: Moderate Hepatic Impairment | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | LSN3106729 | 211 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 251 |
| Abemaciclib: Severe Hepatic Impairment | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | Abemaciclib | 9310 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 49 |
| Abemaciclib: Severe Hepatic Impairment | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | LSN3106729 | 35.3 nanograms*hours/milliliter (ng*h/mL) | — |
| Abemaciclib: Severe Hepatic Impairment | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | LSN2839567 | 846 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 33 |
| Abemaciclib: Severe Hepatic Impairment | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to Infinity(AUC[0-inf]) of Abemaciclib and Active Metabolites | LSN3106726 | 1170 nanograms*hours/milliliter (ng*h/mL) | Geometric Coefficient of Variation 30 |
Primary
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites
Time frame: Day 1: Predose, 1, 2, 3, 4, 6, 8, 10, 24, 48, 72, 96, 120, 144, 168, and 192 Hours Postdose
Population: All participants who received abemaciclib and had evaluable plasma values.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Abemaciclib: Normal Hepatic Function | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | LSN3106729 | 10.4 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
| Abemaciclib: Normal Hepatic Function | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | LSN2839567 | 31.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 57 |
| Abemaciclib: Normal Hepatic Function | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | LSN3106726 | 55.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 40 |
| Abemaciclib: Normal Hepatic Function | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | Abemaciclib | 133 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 63 |
| Abemaciclib: Mild Hepatic Impairment | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | LSN2839567 | 26.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31 |
| Abemaciclib: Mild Hepatic Impairment | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | LSN3106726 | 37.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| Abemaciclib: Mild Hepatic Impairment | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | Abemaciclib | 109 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 65 |
| Abemaciclib: Mild Hepatic Impairment | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | LSN3106729 | 6.24 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27 |
| Abemaciclib: Moderate Hepatic Impairment | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | Abemaciclib | 83.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
| Abemaciclib: Moderate Hepatic Impairment | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | LSN3106726 | 19.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 71 |
| Abemaciclib: Moderate Hepatic Impairment | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | LSN3106729 | 4.96 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 90 |
| Abemaciclib: Moderate Hepatic Impairment | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | LSN2839567 | 13.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 71 |
| Abemaciclib: Severe Hepatic Impairment | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | LSN3106726 | 14.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27 |
| Abemaciclib: Severe Hepatic Impairment | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | LSN3106729 | 2.70 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
| Abemaciclib: Severe Hepatic Impairment | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | Abemaciclib | 156 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 44 |
| Abemaciclib: Severe Hepatic Impairment | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Abemaciclib and Active Metabolites | LSN2839567 | 17.4 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 45 |