Healthy Volunteers
Conditions
Brief summary
The purpose of this study is to determine the effect of baricitinib on the levels of digoxin in the blood stream and how long it takes the body to remove digoxin. This study will also look at how safe and well-tolerated baricitinib is when given at the same time as digoxin in healthy participants. This study will last approximately 3-4 weeks.
Interventions
DRUGBaricitinib
Administered orally
DRUGDigoxin
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
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
* Are overtly healthy males or females, as determined by medical history and physical examination * Women not of child-bearing potential * Menopausal women * Have a body mass index of 18.0 to 29.0 kilograms per square meter (kg/m\^2)
Exclusion criteria
* Women who are lactating * Have previously completed or withdrawn from this study or any other study investigating baricitinib * Currently enrolled in, have completed or discontinued within the last 90 days from a clinical trial involving an investigational product * Have a pulse rate less than 50 beats per minute (bpm) at screening * Have a current or recent history (less than 30 days prior to screening and/or less than 45 days prior to Day -1) of a clinically significant bacterial, fungal, parasitic, viral (not including rhinopharyngitis), or mycobacterial infection * Have an absolute neutrophil count less than 2000 cells/microliter (2×10\^9/liter) at screening or Day -1 * 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 * Intend to use over-the-counter or prescription medication and/or herbal supplements within 14 days prior to dosing and during the study * Have used or intend to use any drugs or substances that are known to be substrates, inducers, or inhibitors of P-glycoprotein (P-gp) within 30 days prior to dosing and throughout the study * Have had symptomatic herpes zoster or herpes simplex infection within 90 days prior to the first dose
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve During 1 Dosing Interval (AUCτ) of Digoxin | Predose up to 24 hours post-dose on Days 7 and 16 |
| PK: Maximum Concentration (Cmax) of Digoxin | Predose up to 24 hours post-dose on Days 7 and 16 |
| PK: Time of Maximum Observed Drug Concentration (Tmax) of Digoxin | Predose up to 24 hours post-dose on Days 7 and 16 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PK: Amount of Drug Excreted Unchanged During 1 Dosing Interval (Aeτ) of Digoxin | 0 to 24 hours post-dose on Days 7 and 16 | — |
| PK: Renal Clearance (CLr) of Digoxin | Predose to 24 hours post-dose on Days 7 and 16 | CLr is the volume of plasma from which study drug is completely removed by the kidney in a given time and is calculated as Aeτ divided by AUCτ. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Baricitinib + Digoxin Digoxin - 0.5 mg administered orally, BID, 12 hours apart on Day 1. Then, 0.25 mg administered orally, QD on Days 2 through 16.
Baricitinib - 10 mg administered orally, QD, immediately prior to digoxin on Days 8 through 16. | 28 |
| Total | 28 |
Baseline characteristics
| Characteristic | Baricitinib + Digoxin |
|---|---|
| Age, Continuous | 33.4 years STANDARD_DEVIATION 11.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Region of Enrollment United Kingdom | 28 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 28 | 6 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 |
Outcome results
Primary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve During 1 Dosing Interval (AUCτ) of Digoxin
Time frame: Predose up to 24 hours post-dose on Days 7 and 16
Population: All enrolled participants who received study drug and had PK data to calculate AUCτ. Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Digoxin Only | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve During 1 Dosing Interval (AUCτ) of Digoxin | 18.7 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 18 |
| Baricitinib + Digoxin | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve During 1 Dosing Interval (AUCτ) of Digoxin | 16.8 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 20 |
Primary
PK: Maximum Concentration (Cmax) of Digoxin
Time frame: Predose up to 24 hours post-dose on Days 7 and 16
Population: All enrolled participants who received study drug and had PK data to calculate Cmax. Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Digoxin Only | PK: Maximum Concentration (Cmax) of Digoxin | 2.04 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 23 |
| Baricitinib + Digoxin | PK: Maximum Concentration (Cmax) of Digoxin | 1.80 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 20 |
Primary
PK: Time of Maximum Observed Drug Concentration (Tmax) of Digoxin
Time frame: Predose up to 24 hours post-dose on Days 7 and 16
Population: All enrolled participants who received study drug and had PK data to calculate tmax. Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Digoxin Only | PK: Time of Maximum Observed Drug Concentration (Tmax) of Digoxin | 1.00 hours (h) |
| Baricitinib + Digoxin | PK: Time of Maximum Observed Drug Concentration (Tmax) of Digoxin | 1.00 hours (h) |
Secondary
PK: Amount of Drug Excreted Unchanged During 1 Dosing Interval (Aeτ) of Digoxin
Time frame: 0 to 24 hours post-dose on Days 7 and 16
Population: All enrolled participants who received study drug and had PK data to calculate Aeτ. Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Digoxin Only | PK: Amount of Drug Excreted Unchanged During 1 Dosing Interval (Aeτ) of Digoxin | 0.177 milligrams (mg) | Geometric Coefficient of Variation 18 |
| Baricitinib + Digoxin | PK: Amount of Drug Excreted Unchanged During 1 Dosing Interval (Aeτ) of Digoxin | 0.155 milligrams (mg) | Geometric Coefficient of Variation 22 |
Secondary
PK: Renal Clearance (CLr) of Digoxin
CLr is the volume of plasma from which study drug is completely removed by the kidney in a given time and is calculated as Aeτ divided by AUCτ.
Time frame: Predose to 24 hours post-dose on Days 7 and 16
Population: All enrolled participants who received study drug and had PK data to calculate CLr. Participants were analyzed based on the treatment they received.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Digoxin Only | PK: Renal Clearance (CLr) of Digoxin | 9.46 Liters/hour (L/h) | Geometric Coefficient of Variation 20 |
| Baricitinib + Digoxin | PK: Renal Clearance (CLr) of Digoxin | 9.20 Liters/hour (L/h) | Geometric Coefficient of Variation 18 |