Healthy Volunteers
Conditions
Brief summary
The purpose of this study is to determine the effects of ciclosporin on the amount of baricitinib that is absorbed into the blood stream and the time it takes to remove baricitinib from the body. The study will also look at how well-tolerated and safe baricitinib is, when given alone and in combination with ciclosporin. Side effects will be documented. The study will last approximately 6 days from the first dose to the end of the study (not including screening or follow-up).
Interventions
DRUGBaricitinib
Administered orally
DRUGCiclosporin
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 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Male participants: agree to use 2 reliable methods of birth control with female partners of childbearing potential during the study and for at least 3 months following the last dose of study drug * Female participants: women not of childbearing potential due to surgical sterilization confirmed by medical history, or menopause * Have a body mass index of 18.0 to 29.0 kilograms per meter squared (kg/m\^2), inclusive * Have clinical laboratory test results within the normal reference range * Have normal renal function * Have normal blood pressure and pulse rate
Exclusion criteria
* Are currently enrolled in a clinical trial involving a study drug or off-label use of a drug or device, or are concurrently enrolled in any other type of medical research * Have completed or discontinued within the last 90 days from a clinical trial involving a study drug * Are participants who have previously completed or withdrawn from this study or any other study investigating baricitinib, and have previously received baricitinib * Have known allergies to baricitinib, ciclosporin, related compounds, or any components of the baricitinib or ciclosporin formulations, or history of significant atopy * Have an abnormality in the 12-lead electrocardiogram (ECG) * Have a history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders * Regularly use known drugs of abuse and/or show positive findings on urinary drug screening * Have a current or recent history of a clinically significant bacterial, fungal, parasitic, viral (not including rhinopharyngitis), or mycobacterial infection * Have had symptomatic herpes zoster or herpes simplex infection within 90 days prior to the first dose * Have an absolute neutrophil count (ANC) less than 2 × 10\^9 cells/liter(L) \[2000 cells/microliter (μL)\] at screening or day prior to first dose of study drug * Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies * Show evidence of hepatitis C infection and/or positive hepatitis C antibody * Show evidence of hepatitis B infection and/or positive hepatitis B surface antigen * Have a history of active tuberculosis within the last 5 years * Are women who are lactating or pregnant * 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 * Intend to use over-the-counter or prescription medication (including salicylate drugs) and/or herbal supplements within 14 days prior to dosing and during the study or intended use of vitamin supplements from Day 1 until discharge from the Clinical Research Unit (CRU) * Have consumed or intend to consume grapefruit, Seville oranges, or products containing these fruits within 7 days prior to the first dose and until discharge from the CRU * Have donated or lost blood of more than 500 milliliters (mL) within the last 3 months * Have an average weekly alcohol intake that exceeds 28 units per week (males) and 21 units per week (females), or are unwilling to stop alcohol consumption from 48 hours prior to the first dose until discharge from the CRU at the end of Period 2 * History of, in the opinion of the investigator, excessive methylxanthine use within the previous 6 months, such as greater than (\>) 6 cups of coffee (or equivalent) per day * Currently smoke more than 10 cigarettes per day
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Baricitinib | Days 1 and 4: predose of baricitinib, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose |
| PK: Area Under the Concentration Curve From Time Zero to Infinity [AUC (0-∞)] of Baricitinib | Days 1 and 4: predose of baricitinib, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose |
| PK: Time of Maximum Observed Drug Concentration (Tmax) of Baricitinib | Days 1 and 4: predose of baricitinib, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose |
Countries
United Kingdom
Participant flow
Pre-assignment details
This was an open-label, 2-period, fixed-sequence study.
Participants by arm
| Arm | Count |
|---|---|
| Baricitinib + Ciclosporin 4 mg baricitinib administered orally on Day 1 of Period 1.
4 mg baricitinib co-administered with 600 mg ciclosporin on Day 4 of Period 2. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Baricitinib + Ciclosporin |
|---|---|
| Age, Continuous | 38.4 years STANDARD_DEVIATION 12.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 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 | 18 Participants |
| Region of Enrollment United Kingdom | 18 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 18 | 15 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 |
Outcome results
Primary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Baricitinib
Time frame: Days 1 and 4: predose of baricitinib, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose
Population: All enrolled participants who received study drug (baricitinib in Period 1 and baricitinib + ciclosporin in Period 2) and had PK data to calculate Cmax of baricitinib.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Baricitinib | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Baricitinib | 36.2 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 25 |
| Baricitinib + Ciclosporin | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Baricitinib | 35.8 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 22 |
Primary
PK: Area Under the Concentration Curve From Time Zero to Infinity [AUC (0-∞)] of Baricitinib
Time frame: Days 1 and 4: predose of baricitinib, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose
Population: All enrolled participants who received study drug (baricitinib in Period 1 and baricitinib + ciclosporin in Period 2) and had PK data to calculate AUC (0-∞) of baricitinib.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Baricitinib | PK: Area Under the Concentration Curve From Time Zero to Infinity [AUC (0-∞)] of Baricitinib | 241 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 24 |
| Baricitinib + Ciclosporin | PK: Area Under the Concentration Curve From Time Zero to Infinity [AUC (0-∞)] of Baricitinib | 311 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 26 |
Primary
PK: Time of Maximum Observed Drug Concentration (Tmax) of Baricitinib
Time frame: Days 1 and 4: predose of baricitinib, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 and 72 hours postdose
Population: All enrolled participants who received study drug (baricitinib in Period 1 and baricitinib + ciclosporin in Period 2) and had PK data to calculate Tmax of baricitinib.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baricitinib | PK: Time of Maximum Observed Drug Concentration (Tmax) of Baricitinib | 1.00 hours |
| Baricitinib + Ciclosporin | PK: Time of Maximum Observed Drug Concentration (Tmax) of Baricitinib | 2.00 hours |