Hepatic Insufficiency, Healthy
Conditions
Brief summary
The main purpose of this study is to measure how much of Imlunestrant (LY3484356) gets into the bloodstream and how long it takes the body to eliminate it in female participants with impaired liver function compared to female participants with normal liver function. The side effects and tolerability of Imlunestrant will also be evaluated. The study may last up to 46 days for each participant.
Interventions
DRUGImlunestrant
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
All Participants: * Women not of childbearing potential may participate and include those who are infertile due to surgical sterilization (hysterectomy, bilateral oophorectomy, bilateral salpingectomy or tubal ligation), congenital anomaly such as mullerian agenesis; or postmenopausal * Are between the body mass index (BMI) of 18.0 and 42.0 kilograms per meter squared (kg/m²), inclusive, at screening Healthy Participants: \- Healthy females as determined by medical history, physical examination, and other screening procedures, with normal liver function Participants with Impaired Liver Function: * Females with chronic mild, moderate and severe liver impairment, assessed by Child-Pugh scoring * Have diagnosis of chronic hepatic impairment (\>6 months), with no clinically significant changes within 90 days prior to study drug administration.
Exclusion criteria
* Women of childbearing potential are excluded from the study. * Have known allergies to imlunestrant or related compounds * Have a history of alcoholism or drug/chemical abuse within 2 years prior to check-in * Have received blood products within 2 months prior to check-in * Have evidence of HIV infection and/or positive human HIV antibodies * Have used or intend to use medications that are strong inhibiters or inducers of cytochrome P450 (CYP)3A4 * Who smoke more than 10 cigarettes or use the equivalent tobacco, smoking-cessation products, nicotine-containing products, or e-cigarettes (nicotine and non-nicotine) per day. * Have a history or presence of cardiovascular (eg, symptomatic bradycardia with resting heart rate of \<60 beats per minute), respiratory, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Imlunestrant | Day 1 (Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post dose) | PK: Cmax of Imlunestrant is reported. |
| PK: Area Under the Concentration-time Curve From 0 to the Last Measurable Concentration (AUC[0-t]) of Imlunestrant | Day 1 (Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post dose) | AUC(0-t) of Imlunestrant is reported. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Imlunestrant (Normal Hepatic Function) Participants received a single dose of Imlunestrant 400 mg administered orally on Day 1 in fasted state. | 9 |
| Imlunestrant (Mild Hepatic Impairment) Participants received a single dose of Imlunestrant 400 mg administered orally on Day 1 in fasted state. | 6 |
| Imlunestrant (Moderate Hepatic Impairment) Participants received a single dose of Imlunestrant 400 mg administered orally on Day 1 in fasted state. | 6 |
| Imlunestrant (Severe Hepatic Impairment) Participants received a single dose of Imlunestrant 200 mg administered orally on Day 1 in fasted state. | 6 |
| Total | 27 |
Baseline characteristics
| Characteristic | Imlunestrant (Normal Hepatic Function) | Total | Imlunestrant (Severe Hepatic Impairment) | Imlunestrant (Moderate Hepatic Impairment) | Imlunestrant (Mild Hepatic Impairment) |
|---|---|---|---|---|---|
| Age, Continuous | 60.3 years STANDARD_DEVIATION 5 | 60.8 years STANDARD_DEVIATION 6 | 57.3 years STANDARD_DEVIATION 3.1 | 59.2 years STANDARD_DEVIATION 8.3 | 66.7 years STANDARD_DEVIATION 3.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 15 Participants | 3 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 12 Participants | 3 Participants | 3 Participants | 1 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 | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 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 | 8 Participants | 25 Participants | 6 Participants | 5 Participants | 6 Participants |
| Region of Enrollment United States | 9 Participants | 27 Participants | 6 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Female | 9 Participants | 27 Participants | 6 Participants | 6 Participants | 6 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 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 | 0 / 9 | 0 / 6 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 0 / 9 | 0 / 6 | 2 / 6 | 2 / 6 |
| serious Total, serious adverse events | 0 / 9 | 0 / 6 | 1 / 6 | 0 / 6 |
Outcome results
Primary
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Imlunestrant
PK: Cmax of Imlunestrant is reported.
Time frame: Day 1 (Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post dose)
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Imlunestrant (Normal Hepatic Function) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Imlunestrant | 58.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 56 |
| Imlunestrant (Mild Hepatic Impairment) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Imlunestrant | 74.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
| Imlunestrant (Moderate Hepatic Impairment) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Imlunestrant | 87.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 51 |
| Imlunestrant (Severe Hepatic Impairment) | Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of Imlunestrant | 46.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49 |
Primary
PK: Area Under the Concentration-time Curve From 0 to the Last Measurable Concentration (AUC[0-t]) of Imlunestrant
AUC(0-t) of Imlunestrant is reported.
Time frame: Day 1 (Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240 hours post dose)
Population: All participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Imlunestrant (Normal Hepatic Function) | PK: Area Under the Concentration-time Curve From 0 to the Last Measurable Concentration (AUC[0-t]) of Imlunestrant | 1970 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 51 |
| Imlunestrant (Mild Hepatic Impairment) | PK: Area Under the Concentration-time Curve From 0 to the Last Measurable Concentration (AUC[0-t]) of Imlunestrant | 2410 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 27 |
| Imlunestrant (Moderate Hepatic Impairment) | PK: Area Under the Concentration-time Curve From 0 to the Last Measurable Concentration (AUC[0-t]) of Imlunestrant | 4320 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 50 |
| Imlunestrant (Severe Hepatic Impairment) | PK: Area Under the Concentration-time Curve From 0 to the Last Measurable Concentration (AUC[0-t]) of Imlunestrant | 2820 nanograms*hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 47 |