Healthy Volunteers
Conditions
Brief summary
The purposes of this study are to determine the effects of baricitinib on the time it takes to remove simvastatin from the body and to look at how well-tolerated and safe baricitinib is when given alone and in combination with simvastatin. Side effects will be documented. The study will last approximately 7 days from the first dose to the end of the study (not including screening or follow-up).
Interventions
DRUGBaricitinib
Administered orally
DRUGSimvastatin
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or discontinued within the last 90 days from a clinical trial involving a study drug * Have previously completed or withdrawn from this study or any other study investigating baricitinib, and have previously received baricitinib * Have known allergies to baricitinib, simvastatin, related compounds, or any components of the baricitinib or simvastatin 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 (including hypothyroidism), hematological, or neurological disorders * Have current or recent history of myalgia or muscle weakness * 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/liters (L) \[2000 cells/microliter (μL)\] at screening or day prior to first dose of study drug. For abnormal values, a single repeat will be allowed * 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 * Are women who are lactating * 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 or grapefruit-containing products within 14 days prior to the first dose and throughout the study * 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 | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum Concentration (Cmax) of Simvastatin and Simvastatin Acid | Period 1, Day 1 and Period 2, Day 6: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours postdose | The Cmax of simvastatin \[a cytochrome P450 (CYP) 3A substrate\] and its active acid metabolite (simvastatin acid) is reported. |
| PK: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] of Simvastatin and Simvastatin Acid | Period 1, Day 1 and Period 2, Day 6: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours postdose | The AUC(0-∞) of simvastatin (a CYP3A substrate) and its active acid metabolite (simvastatin acid) is reported. |
Countries
United Kingdom
Participant flow
Pre-assignment details
This was an open-label, fixed-sequence, 2-period study of healthy participants.
Participants by arm
| Arm | Count |
|---|---|
| Simvastatin Then Baricitinib and Simvastatin Period 1: 40-mg tablet of simvastatin administered orally on Day 1.
Period 2: 10-mg dose of baricitinib (2 × 4-mg and 1 × 2-mg tablets) administered orally QD on Days 3 through 7, with coadministration of 40-mg simvastatin tablet on Day 6. | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Period 2 (Days 3-18) | Adverse Event | 2 |
Baseline characteristics
| Characteristic | Simvastatin Then Baricitinib and Simvastatin |
|---|---|
| Age, Continuous | 40.0 years STANDARD_DEVIATION 13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 40 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 | 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 | 39 Participants |
| Region of Enrollment United Kingdom | 40 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 35 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 / 40 | 1 / 40 | 3 / 38 |
| serious Total, serious adverse events | 0 / 40 | 0 / 40 | 0 / 38 |
Outcome results
Primary
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Simvastatin and Simvastatin Acid
The Cmax of simvastatin \[a cytochrome P450 (CYP) 3A substrate\] and its active acid metabolite (simvastatin acid) is reported.
Time frame: Period 1, Day 1 and Period 2, Day 6: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours postdose
Population: Participants who received study drug (simvastatin in Period 1 and at least 1 dose of baricitinib and simvastatin in Period 2) and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Simvastatin | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Simvastatin and Simvastatin Acid | Simvastatin | 6.85 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 74 |
| Simvastatin | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Simvastatin and Simvastatin Acid | Simvastatin Acid | 1.93 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 68 |
| Baricitinib and Simvastatin | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Simvastatin and Simvastatin Acid | Simvastatin | 4.65 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 57 |
| Baricitinib and Simvastatin | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Simvastatin and Simvastatin Acid | Simvastatin Acid | 1.60 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 50 |
Primary
PK: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] of Simvastatin and Simvastatin Acid
The AUC(0-∞) of simvastatin (a CYP3A substrate) and its active acid metabolite (simvastatin acid) is reported.
Time frame: Period 1, Day 1 and Period 2, Day 6: Predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24 and 48 hours postdose
Population: Participants who received study drug (simvastatin in Period 1 and at least 1 dose of baricitinib and simvastatin in Period 2) and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Simvastatin | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] of Simvastatin and Simvastatin Acid | Simvastatin (n=39, 36) | 40.7 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 86 |
| Simvastatin | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] of Simvastatin and Simvastatin Acid | Simvastatin Acid (n=33, 32) | 26.4 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 81 |
| Baricitinib and Simvastatin | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] of Simvastatin and Simvastatin Acid | Simvastatin (n=39, 36) | 33.7 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 75 |
| Baricitinib and Simvastatin | PK: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] of Simvastatin and Simvastatin Acid | Simvastatin Acid (n=33, 32) | 21.0 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 64 |