Healthy Volunteers
Conditions
Brief summary
The purposes of this study are to look at what effect multiple doses of rifampicin have on a single dose of baricitinib and to look at the safety and tolerability of these drugs. Side effects will be documented. The study will last approximately 31 days from the first dose to the end of the study.
Interventions
DRUGBaricitinib
Administered orally
DRUGRifampicin
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
* Are overtly healthy males or females * 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 (at least 3 months after surgical hysterectomy, bilateral oophorectomy with or without hysterectomy, or bilateral tubal occlusion/ligation) confirmed by medical history, or menopause. Menopausal women are women with spontaneous amenorrhea for at least 12 months, not induced by a medical condition such as anorexia nervosa and not taking medications during the amenorrhea that induced the amenorrhea (for example, oral contraceptives, hormones, gonadotropin releasing hormone, anti-estrogens, selective estrogen receptor modulators, or chemotherapy). Menopausal status should be confirmed by a follicle-stimulating hormone (FSH) level greater than 40 international units per liter (IU/L) at screening \[unless the participant is taking hormone replacement therapy (HRT)\] * Have a body weight of ≥60 kilograms (kg) at the time of screening * Have clinical laboratory test results within normal reference range * Have normal renal function * Have normal blood pressure and pulse rate (supine position) * Have venous access sufficient to allow for blood sampling
Exclusion criteria
* Are currently enrolled in, have completed, or discontinued within the last 90 days from a clinical trial involving a study drug, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study * Have previously completed or withdrawn from this study or any other study investigating baricitinib, and have previously received the study drug * Have known allergies to baricitinib, rifampicin, related compounds, or any components of the baricitinib or rifampicin formulations, or history of significant atopy * Have a history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders * 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 48 hours prior to the first dose and until completion of the safety follow-up assessment \[Day 18 ± 1; 1 unit = 12 ounces (oz) or 360 milliliters (mL) of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits\] * Have a history of, in the opinion of the investigator, excessive methylxanthine use within previous 6 months, such as greater than (\>)6 cups of coffee (or equivalent) per day * Currently smoke more than 10 cigarettes per day or are unable to abide by Clinical Research Unit (CRU) restrictions * Are unwilling to refrain from using soft contact lenses from the start of the second treatment period until after the final follow-up
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PK: Maximum Concentration (Cmax) of Baricitinib | Period 1, Day 1 and Period 2, Day 10: Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose |
| PK: Area Under the Concentration Versus Time Curve From 0 to Infinity [AUC(0-∞)] of Baricitinib | Period 1, Day 1 and Period 2, Day 10: Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose |
| PK: Time of Maximum Observed Drug Concentration (Tmax) of Baricitinib | Period 1, Day 1 and Period 2, Day 10: Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose |
Countries
United Kingdom
Participant flow
Pre-assignment details
This was an open-label, fixed-sequence, 2-period study conducted in healthy participants to compare the single dose pharmacokinetics (PK) of baricitinib when given alone and when coadministered with rifampicin.
Participants by arm
| Arm | Count |
|---|---|
| Baricitinib Then Baricitinib and Rifampicin Period 1: 10-mg dose of baricitinib (2 x 4-mg and 1 x 2-mg tablets) administered orally on Day 1.
Period 2: 600-mg dose of rifampicin (2 x 300-mg capsules) administered orally QD on Days 3 through 11, with coadministration of a 10-mg dose of baricitinib on Day 10. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Baricitinib Then Baricitinib and Rifampicin |
|---|---|
| Age, Continuous | 40.9 years STANDARD_DEVIATION 15.4 |
| 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 | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 16 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 | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 18 | 3 / 18 | 5 / 18 |
| serious Total, serious adverse events | 0 / 18 | 0 / 18 | 0 / 18 |
Outcome results
Primary
PK: Area Under the Concentration Versus Time Curve From 0 to Infinity [AUC(0-∞)] of Baricitinib
Time frame: Period 1, Day 1 and Period 2, Day 10: Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose
Population: Participants who received study drug (baricitinib in Period 1 and at least 1 dose of rifampicin and baricitinib in Period 2) and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Baricitinib | PK: Area Under the Concentration Versus Time Curve From 0 to Infinity [AUC(0-∞)] of Baricitinib | 634 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 19 |
| Baricitinib and Rifampicin | PK: Area Under the Concentration Versus Time Curve From 0 to Infinity [AUC(0-∞)] of Baricitinib | 416 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 20 |
Primary
PK: Maximum Concentration (Cmax) of Baricitinib
Time frame: Period 1, Day 1 and Period 2, Day 10: Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose
Population: Participants who received study drug (baricitinib in Period 1 and at least 1 dose of rifampicin and baricitinib in Period 2) and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Baricitinib | PK: Maximum Concentration (Cmax) of Baricitinib | 96.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 22 |
| Baricitinib and Rifampicin | PK: Maximum Concentration (Cmax) of Baricitinib | 101 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
Primary
PK: Time of Maximum Observed Drug Concentration (Tmax) of Baricitinib
Time frame: Period 1, Day 1 and Period 2, Day 10: Predose, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, and 48 hours postdose
Population: Participants who received study drug (baricitinib in Period 1 and at least 1 dose of rifampicin and baricitinib in Period 2) and who had evaluable PK data.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Baricitinib | PK: Time of Maximum Observed Drug Concentration (Tmax) of Baricitinib | 1.00 hours (h) |
| Baricitinib and Rifampicin | PK: Time of Maximum Observed Drug Concentration (Tmax) of Baricitinib | 1.00 hours (h) |