Arthritis, Rheumatoid, Chronic Inflammatory Disorder
Conditions
Brief summary
The purpose of this trial is to assess the effect of 3 formulations on the relative bioavailability of LY3009104. Participants will receive single dose of LY3009104 on 4 separate occasions with and without food. Safety evaluation and serial pharmacokinetic (PK) samples will be collected during each treatment period. Approximately 5 to 7 days of washout period between each treatment and a follow-up visit will occur approximately 5 to 7 days after the last dose of study drug.
Interventions
DRUGLY3009104
Administered orally
Sponsors
Incyte Corporation
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Overtly healthy males or females as determined by medical history and physical examination * Have a body mass index (BMI) of 18.5 to 29.9 kilograms per square meter (kg/m\^2), 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 normal blood pressure and pulse rate as determined by the investigator * Have venous access sufficient to allow for blood sampling * Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures * Have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site Male Participants: * Agree to use two forms of highly effective methods of birth control \[oral, injectable, or implanted hormonal contraceptives; condom with spermicidal foam/gel/film/cream/suppository; occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; intrauterine device; intrauterine system, for example, progestin releasing coil; and vasectomised male (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate)\] with female partners of childbearing potential during the study and for at least 3 months following the last dose of study drug Female participants: * Are women of non-childbearing potential, defined as: women with Mayer Rokitansky Kuster Hauser Syndrome (also referred to as Clinical Absence of Uterus and Vagina), or women who have had surgical sterilization (hysterectomy or bilateral oophorectomy or tubal ligation), or women greater than 60 years of age, or women greater than 40 and less than 60 years of age who have had a cessation of menses for at least 12 months and a follicle-stimulating hormone (FSH) test confirming non-childbearing potential \[FSH ≥40 milli-international units per milliliter (mIU/mL)\]
Exclusion criteria
* Are currently enrolled in, or have completed or discontinued within the last 30 days from, a clinical trial involving an investigational product, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study * Have a history of adverse drug reactions or drug allergy to more than 3 types of systemically administered medications (all penicillins and cephalosporins may be considered 1 type of medication for this purpose) * Are participants who have previously received the investigational product in this study, have completed or withdrawn from this study or any other study investigating LY3009104 * Have an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, increases the risks associated with participating in the study * Current or recent history (\<30 days prior to screening and/or \<45 days prior to Check-in) of a clinically significant bacterial, fungal, parasitic, viral (not including rhinopharyngitis), or mycobacterial infection * Have an absolute neutrophil count (ANC) less than 2000 cells per microliter (cell/μL). For abnormal values, a single repeat will be allowed * 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 * Regularly use known drugs of abuse * Have had symptomatic herpes zoster or herpes simplex infection within 90 days prior to the first dose * 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 * Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies * Show evidence of hepatitis C and/or positive hepatitis C antibody * Show evidence of hepatitis B and/or positive hepatitis B surface antigen * Intend to use over-the-counter or prescription medication and herbal supplements within 14 days prior to dosing and during the study * Intend to use vitamins and mineral supplements within 2 days prior to dosing and during the study * Have donated blood of more than 450 milliliters (mL) within the previous 3 months * Have consumed grapefruit, starfruit, pomelos, or products containing these fruits, 7 days prior to the first dose and during the study * Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females), or are unwilling to stop alcohol consumption for 48 hours prior to admission in each period until the 48 hour PK sample has been collected \[1 unit = 12 ounces (oz) or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits\] * Have used any tobacco-containing or nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patches, nicotine lozenges, or nicotine gum) within 6 months prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Plasma Concentration-Time Curve (AUC) | Predose up to 48 hours postdose for each of the 4 treatment periods | The area under the concentration-time curve from time 0 to infinity \[AUC(0-inf)\] is reported for participants who received either LY3009104 tablets or capsules in a fasted or fed state. |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Maximum Plasma Concentration (Cmax) | Predose up to 48 hours postdose for each of the 4 treatment periods |
| Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) | Predose up to 48 hours postdose for each of the 4 treatment periods |
Countries
Singapore
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes groups randomized to receive any of the following study drugs as the first intervention.
LY3009104 Reference Formulation (RF): 8-milligram (mg) dose of LY3009104 RF (two 4-mg phosphate salt capsules) administered once in a fasted state.
LY3009104 Test Formulation 1 (TF1), 20 micrometers (mcm): 8-mg dose of LY3009104 TF1 \[one 8-mg tablet, free base formulation, target active pharmaceutical ingredient (API) particle size of 20 mcm\] administered once in a fasted state.
LY3009104 Test Formulation 2 (TF2), 50 mcm, fasted: 8-mg dose of LY3009104 TF2 (one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once in a fasted state.
LY3009104 TF2, 50 mcm, fed: 8-mg dose of LY3009104 TF2 (one 8-mg tablet, free base formulation, target API particle size of 50 mcm) administered once with a high-fat, high calorie meal. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 38.0 years STANDARD_DEVIATION 9.6 |
| Race/Ethnicity, Customized Asian | 14 participants |
| Race/Ethnicity, Customized White | 1 participants |
| Region of Enrollment Singapore | 15 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 14 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 | 1 / 15 | 5 / 15 | 2 / 15 | 2 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 | 0 / 15 | 0 / 15 |
Outcome results
Primary
Pharmacokinetics: Plasma Concentration-Time Curve (AUC)
The area under the concentration-time curve from time 0 to infinity \[AUC(0-inf)\] is reported for participants who received either LY3009104 tablets or capsules in a fasted or fed state.
Time frame: Predose up to 48 hours postdose for each of the 4 treatment periods
Population: Randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY3009104 Reference Formulation | Pharmacokinetics: Plasma Concentration-Time Curve (AUC) | 1670 nanomoles*hours per liter (nmol*h/L) | Geometric Coefficient of Variation 35 |
| LY3009104 Test Formulation 1 (20-mcm) | Pharmacokinetics: Plasma Concentration-Time Curve (AUC) | 1710 nanomoles*hours per liter (nmol*h/L) | Geometric Coefficient of Variation 32 |
| LY3009104 Test Formulation 2 (50-mcm, Fed) | Pharmacokinetics: Plasma Concentration-Time Curve (AUC) | 1510 nanomoles*hours per liter (nmol*h/L) | Geometric Coefficient of Variation 34 |
| LY3009104 Test Formulation 2 (50-mcm, Fasted) | Pharmacokinetics: Plasma Concentration-Time Curve (AUC) | 1700 nanomoles*hours per liter (nmol*h/L) | Geometric Coefficient of Variation 35 |
90% CI: [0.951, 1.1]
90% CI: [0.947, 1.09]
90% CI: [0.827, 0.953]
Secondary
Pharmacokinetics: Maximum Plasma Concentration (Cmax)
Time frame: Predose up to 48 hours postdose for each of the 4 treatment periods
Population: Randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| LY3009104 Reference Formulation | Pharmacokinetics: Maximum Plasma Concentration (Cmax) | 259 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 26 |
| LY3009104 Test Formulation 1 (20-mcm) | Pharmacokinetics: Maximum Plasma Concentration (Cmax) | 253 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 19 |
| LY3009104 Test Formulation 2 (50-mcm, Fed) | Pharmacokinetics: Maximum Plasma Concentration (Cmax) | 205 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 27 |
| LY3009104 Test Formulation 2 (50-mcm, Fasted) | Pharmacokinetics: Maximum Plasma Concentration (Cmax) | 250 nanomoles per liter (nmol/L) | Geometric Coefficient of Variation 30 |
90% CI: [0.868, 1.1]
90% CI: [0.852, 1.08]
90% CI: [0.727, 0.925]
Secondary
Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax)
Time frame: Predose up to 48 hours postdose for each of the 4 treatment periods
Population: Randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LY3009104 Reference Formulation | Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) | 1.00 hours (h) |
| LY3009104 Test Formulation 1 (20-mcm) | Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) | 1.00 hours (h) |
| LY3009104 Test Formulation 2 (50-mcm, Fed) | Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) | 2.00 hours (h) |
| LY3009104 Test Formulation 2 (50-mcm, Fasted) | Pharmacokinetics: Time to Maximum Plasma Concentration (Tmax) | 1.00 hours (h) |
p-value: 0.71990% CI: [-0.25, 0.5]Wilcoxon (Mann-Whitney)
p-value: 0.9690% CI: [-0.25, 0.75]Wilcoxon (Mann-Whitney)
p-value: 0.00690% CI: [0, 2]Wilcoxon (Mann-Whitney)