Healthy
Conditions
Brief summary
The main purpose of this study is to investigate the safety and tolerability of the study drug known as baricitinib in healthy Chinese participants. The study will measure how the body absorbs, breaks down and gets rid of baricitinib. The study will last about 20 days, not including screening. This study is for research purposes only, and is not intended to treat any medical condition.
Interventions
DRUGBaricitinib
Administered orally.
DRUGPlacebo
Administered orally.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Are overtly healthy Chinese males agreed to use methods of birth control or are postmenopausal Chinese females, as determined by medical history and physical examination * Have a body mass index of 19.0 to 24.0 kilograms per meter squared (kg/m²), inclusive, at screening. * 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. * Have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site.
Exclusion criteria
* Have a history of adverse drug reactions or drug allergy to more than 3 types of systemically administered medications. * 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 capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data. * Have a history of stomach or intestinal surgery. * Current or recent history (\<30 days prior to screening of a clinically significant bacterial, fungal, parasitic, viral (not including rhinopharyngitis), or mycobacterial infection. * Have an absolute neutrophil count (ANC) less than 2000 cell/microliter (μL) (2 x 109/liter \[L\]). * Have current herpes zoster or simplex within 90 days prior to the first dose, * Have evidence of active or latent tuberculosis (TB) * Have used or intend to use over-the-counter, prescription medication, or Chinese herbal preparation within 14 days prior to dosing and during the study. * Have consumed grapefruit, grapefruit juice, or grapefruit products within 7 days prior to the first dose or are unwilling to abide by the grapefruit restrictions during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Clinically Significant Event(s) | Baseline through Study Completion (up to Day 20) | Clinically significant events were defined as a moderate to severe adverse event, abnormal clinical sign, or clinical laboratory finding that may pose risk to the well-being of the participant. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics(PK): Maximum Concentration (Cmax) of Baricitinib | Day 1: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Postdose; Day 5: Predose; Day 6: Predose; Day 7: Predose; Day 8: Predose; Day 9: Predose; Day 10: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Postdose | Maximum observed drug concentration for single dose and Cmax as steady date for multiple dosing. |
| Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of Baricitinib | Day 1: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Postdose; Day 5: Predose; Day 6: Predose; Day 7: Predose; Day 8: Predose; Day 9: Predose; Day 10: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Postdose | Area under the concentration versus time curve from zero to infinity (AUC0-inf) during single dose and area under the concentration versus time curve (AUCtau,ss) during multiple dose of baricitinib at steady state. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo matching baricitinib administered orally, once on Day 1 and once a day (QD) on Days 4 through 10 (7 days). | 8 |
| 2mg Baricitinib 2mg baricitinib administered orally, once on Day 1 and once a day (QD) on Days 4 through 10 (7 days). | 8 |
| 4mg Baricitinib 4mg baricitinib administered orally, once on Day 1 and once a day (QD) on Days 4 through 10 (7 days). | 9 |
| 10mg Baricitinib 10mg baricitinib administered orally, once on Day 1 and once a day (QD) on Days 4 through 10 (7 days). | 8 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Treatment | Physician and Sponsor Decision | 1 | 0 | 0 | 0 |
| Treatment | Withdrawal by Subject | 1 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | 2mg Baricitinib | 4mg Baricitinib | 10mg Baricitinib | Total |
|---|---|---|---|---|---|
| Age, Continuous | 26.6 years STANDARD_DEVIATION 5.4 | 30.8 years STANDARD_DEVIATION 7.3 | 26.6 years STANDARD_DEVIATION 3.5 | 27.6 years STANDARD_DEVIATION 6.7 | 27.8 years STANDARD_DEVIATION 5.8 |
| Body Mass Index (BMI) | 22.34 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.21 | 22.15 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.75 | 21.87 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.28 | 21.68 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.39 | 22.01 kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.38 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 8 Participants | 8 Participants | 9 Participants | 8 Participants | 33 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment China | 8 Participants | 8 Participants | 9 Participants | 8 Participants | 33 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 8 Participants | 9 Participants | 8 Participants | 33 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 | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 8 | 1 / 8 | 2 / 9 | 4 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 9 | 0 / 8 |
Outcome results
Primary
Number of Participants With One or More Clinically Significant Event(s)
Clinically significant events were defined as a moderate to severe adverse event, abnormal clinical sign, or clinical laboratory finding that may pose risk to the well-being of the participant. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Event module.
Time frame: Baseline through Study Completion (up to Day 20)
Population: All randomized participants who received at least one dose of study drug and experienced clinically significant event.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With One or More Clinically Significant Event(s) | 4 Participants |
| 2mg Baricitinib | Number of Participants With One or More Clinically Significant Event(s) | 0 Participants |
| 4mg Baricitinib | Number of Participants With One or More Clinically Significant Event(s) | 2 Participants |
| 10mg Baricitinib | Number of Participants With One or More Clinically Significant Event(s) | 4 Participants |
Secondary
Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of Baricitinib
Area under the concentration versus time curve from zero to infinity (AUC0-inf) during single dose and area under the concentration versus time curve (AUCtau,ss) during multiple dose of baricitinib at steady state.
Time frame: Day 1: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Postdose; Day 5: Predose; Day 6: Predose; Day 7: Predose; Day 8: Predose; Day 9: Predose; Day 10: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Postdose
Population: All randomized participants who received at least 1 dose of baricitinib and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of Baricitinib | Single Dose Day 1 | 139 nanogram * hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 12 |
| Placebo | Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of Baricitinib | Multiple Dose Day 10 | 145 nanogram * hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 12 |
| 2mg Baricitinib | Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of Baricitinib | Single Dose Day 1 | 270 nanogram * hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 17 |
| 2mg Baricitinib | Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of Baricitinib | Multiple Dose Day 10 | 265 nanogram * hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 18 |
| 4mg Baricitinib | Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of Baricitinib | Multiple Dose Day 10 | 771 nanogram * hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 14 |
| 4mg Baricitinib | Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of Baricitinib | Single Dose Day 1 | 777 nanogram * hour per milliliter (ng*h/mL) | Geometric Coefficient of Variation 9 |
Secondary
Pharmacokinetics(PK): Maximum Concentration (Cmax) of Baricitinib
Maximum observed drug concentration for single dose and Cmax as steady date for multiple dosing.
Time frame: Day 1: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Postdose; Day 5: Predose; Day 6: Predose; Day 7: Predose; Day 8: Predose; Day 9: Predose; Day 10: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, and 48 hours Postdose
Population: All randomized participants who received at least one dose of baricitinib and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics(PK): Maximum Concentration (Cmax) of Baricitinib | Single Dose Day 1 | 24.3 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 17 |
| Placebo | Pharmacokinetics(PK): Maximum Concentration (Cmax) of Baricitinib | Multiple Dose Day 10 | 28.0 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 24 |
| 2mg Baricitinib | Pharmacokinetics(PK): Maximum Concentration (Cmax) of Baricitinib | Single Dose Day 1 | 47.8 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 42 |
| 2mg Baricitinib | Pharmacokinetics(PK): Maximum Concentration (Cmax) of Baricitinib | Multiple Dose Day 10 | 48.0 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
| 4mg Baricitinib | Pharmacokinetics(PK): Maximum Concentration (Cmax) of Baricitinib | Single Dose Day 1 | 147 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 28 |
| 4mg Baricitinib | Pharmacokinetics(PK): Maximum Concentration (Cmax) of Baricitinib | Multiple Dose Day 10 | 136 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 17 |