Hepatic Insufficiency, Liver Diseases
Conditions
Brief summary
The main purpose of this study is to measure how much of the study drug called baricitinib gets into the blood stream and how long it takes the body to get rid of it. Healthy participants and those with liver disease may enroll. The study will last about 7 days for each participant, not including screening.
Interventions
DRUGBaricitinib
Administered orally
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 70 Years
Healthy volunteers
Yes
Inclusion criteria
for ALL Participants: * Male participants agree to use 2 reliable methods of birth control with female partners of child-bearing potential during the study and for at least 3 months following the last dose of study drug * Women not of child-bearing potential due to surgical sterilization (at least 6 weeks after surgical bilateral oophorectomy with or without hysterectomy or at least 6 weeks after confirmed tubal occlusion/tubal ligation) confirmed by medical history or menopause * Menopausal women with spontaneous amenorrhea for at least 12 months, not induced by a medical condition and by medications and have a follicle-stimulating hormone (FSH) level greater than 40 milli-international units per milliliter (mIU/mL) (unless the participant is taking hormone replacement therapy \[HRT\]) * Have a body mass index of 18.5 to 40.0 kilograms per square meter (kg/m\^2) inclusive at the time of screening Additional Inclusion Criteria for Healthy Participants: * Are overtly healthy participants, have normal hepatic function and have stable chronic medical conditions * Have clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator Additional Inclusion Criteria for Hepatically Impaired Participants: * Participants with hepatic impairment classified as Child-Pugh score A or B (mild \[Group 3, if enrolled\] or moderate \[Group 2\] impairment, respectively). Must have a diagnosis of chronic hepatic impairment (greater than 6 months), with no clinically significant changes within 90 days prior to study drug administration (Day 1). Participants may have mild stable baseline medical conditions for which neither the condition nor treatments received would negatively impact the health of the participant or study conduct * Clinical laboratory test results with deviations that are judged by the investigator to be compatible with the hepatic impairment of the participant, or of no additional clinical significance for this study
Exclusion criteria
for ALL Participants: * Have received, within the last 30 days, an investigational product as part of a clinical trial, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study * Persons who have previously completed or withdrawn from study investigating baricitinib, and have previously received the investigational product * Women with a positive pregnancy test or who are lactating * Have a current or recent history (less than 30 days prior to screening and/or less than 45 days prior to admission to the clinical research unit) of a clinically significant bacterial, fungal, parasitic, viral (excluding rhinopharyngitis), or mycobacterial infection * Have had symptomatic herpes zoster or herpes simplex infection within 90 days prior to the first dose * Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies * Have been exposed to a live vaccine within 12 weeks prior to the first dose or expected to need/receive a live vaccine (including herpes zoster vaccination) during the course of the study Additional
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Baricitinib (LY3009104) | Predose up to 48 hours (h) postdose |
| PK: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] of Baricitinib | Predose up to 48 h postdose |
Countries
United States
Participant flow
Pre-assignment details
An interim analysis was to be performed after ≤6 participants (pts) each in Group (G) 1 and G2 completed the study. If a \<1.3-fold difference in exposure was seen between pts with moderate hepatic impairment (G2) and pts with normal hepatic function (G1), then pts with mild hepatic impairment (G3) were not to be enrolled. No pt was enrolled in G3.
Participants by arm
| Arm | Count |
|---|---|
| Baricitinib (Healthy Participants) Group 1: A single 4-mg dose of baricitinib (one 4-mg tablet) administered once, orally, to participants with normal hepatic function. | 8 |
| Baricitinib (Moderate Hepatic Impairment) Group 2: A single 4-mg dose of baricitinib (one 4-mg tablet) administered once, orally, to participants with moderate hepatic impairment as classified by Child-Pugh B. | 8 |
| Total | 16 |
Baseline characteristics
| Characteristic | Baricitinib (Healthy Participants) | Baricitinib (Moderate Hepatic Impairment) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 8 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 3 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 5 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 8 Participants | 15 Participants |
| Region of Enrollment United States | 8 Participants | 8 Participants | 16 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 8 | 4 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 |
Outcome results
Primary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Baricitinib (LY3009104)
Time frame: Predose up to 48 hours (h) postdose
Population: Participants who received 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Baricitinib (Healthy Participants) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Baricitinib (LY3009104) | 35.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| Baricitinib (Moderate Hepatic Impairment) | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Baricitinib (LY3009104) | 38.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 23 |
Primary
PK: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] of Baricitinib
Time frame: Predose up to 48 h postdose
Population: Participants who received 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Baricitinib (Healthy Participants) | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] of Baricitinib | 295 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 25 |
| Baricitinib (Moderate Hepatic Impairment) | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] of Baricitinib | 350 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 28 |