A Study of LY3009104(Baricitinib) for Healthy Subjects

Study Overview
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Brief Summary
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To evaluate the safety and tolerability of LY3009104 when given orally as single and multiple doses in Japanese healthy subjects.

Official Title
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A Single- and Multiple-Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LY3009104 in Japanese Healthy Subjects

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Drug: LY3009104
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or females. Male subjects: Agree to use 2 forms of highly effective methods of birth control with female partners of childbearing potential for the specified duration. Female subjects: Females must not be pregnant, breastfeeding, or at risk to become pregnant during study participation. Female subjects of childbearing potential must test negative for pregnancy at screening and agree to use 2 forms of highly effective methods of birth control, or remain abstinent for the specified duration. Up to third generation Japanese, that is defined as all of the subject's biological grandparents are of exclusive Japanese decent and have been born in Japan. Are between the body mass index (BMI) of 18.0 and 30.0 kg/m², inclusive at screening. Exclusion Criteria: Are subjects who have previously completed or withdrawn from this study or any other study investigating LY3009104, and received the study drug. 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. Show evidence of significant active neuropsychiatric disease. Have current or recent history of herpes zoster or simplex in the last 90 days prior to randomization, or history of herpes zoster, such as disseminated herpes zoster involving multiple dermatomes, ocular involvement, including herpes zoster involving the ophthalmic branch of the trigeminal nerve. Have or have a history of rheumatoid arthritis. History of malignancy, with the exception of cured basal cell or squamous cell carcinoma of the skin. History of stomach or intestinal surgery, except that appendectomy and/or cholecystectomy will be allowed. Receipt of blood products within 2 months prior to study entry.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2 mg LY3009104 (Cohort 1)<br>2mg administered once on day 1 (single dose) | Drug: LY3009104<br>* Administered orally<br>* Other names: baricitinib;|
| Experimental: 5 mg LY3009104 (Cohort 2)<br>5mg administered once on day 1 (single dose) | Drug: LY3009104<br>* Administered orally<br>* Other names: baricitinib;|
| Experimental: 10 mg LY3009104 (Cohort 3)<br>10 mg administered on day 1 (single dose) and following a 7 day washout period, administered once daily for 10 days (multiple dose) | Drug: LY3009104<br>* Administered orally<br>* Other names: baricitinib;|
| Experimental: 14 mg LY3009104 (Cohort 4 )<br>14 mg administered on day 1 (single dose) and following a 7 day washout period, administered once daily for 10 days (multiple dose) | Drug: LY3009104<br>* Administered orally<br>* Other names: baricitinib;|
| Placebo Comparator: Placebo<br>administered on day 1 (single dose) and following a 7 day washout period, administered once daily for 10 days (multiple dose) | Drug: Placebo<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinically Significant Effects | Adverse events were considered clinically significant effects. A summary of serious adverse events and other nonserious adverse events are located in the Reported Adverse Event section. | Days 1-10 for Cohorts 1 & 2, Days 1-7 for single dose of Cohorts 3 & 4, Days 8-31 for multiple doses | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY3009104 | Cmax of Day 1 is Cmax after single dose, and Cmax of Day 17 is Cmax at steady-state. | Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose | 
| Pharmacokinetics: Area Under the Concentration Versus Time Curve (AUC) of LY3009104 | AUC is the measure of total plasma exposure of a drug over a given time period. AUC of Day 1 is AUC from 0 to 24 hours. AUC of Day 17 is AUC during one dosing interval at steady-state. | Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose | 
| Pharmacokinetics: Half-Life(t1/2) of LY3009104 | Half life (t1/2) is the time measured for the plasma concentration of LY3009104 to decrease by one half. | Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose | 
| Pharmacokinetics: Apparent Volume of Distribution of LY3009104 | Apparent volume of distribution is used to quantify the distribution of a drug between plasma and the rest of the body after dosing. It is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Day 1, it is apparent volume of distribution during the terminal phase after single dose. Day 17, it is apparent volume of distribution during the terminal phase at steady-state. | Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours postdose | 
| Pharmacokinetics: Apparent Total Body Clearance of LY3009104 | Apparent total body clearance is the volume of plasma from which the drug is completely removed in a given time period. For Day 1, it is apparent total body clearance of drug after single dose. For Day 17, it is apparent total body clearance of drug at steady-state. | Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 38 and 48 hours postdose | 
| Pharmacokinetics: Time of Maximum Observed LY3009104 Concentration (Tmax) | Tmax is time to reach maximum observed drug concentration. For Day 1, it is tmax after single dose. For Day 17, it is tmax at steady-state. | Day 1 and Day 17: predose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 38 and 48 hours postdose | 
| Pharmacokinetics: Renal Excretion of LY3009104 | Percentage of LY3009104 excreted in urine from zero to 24 hours. | Day 1: continuous for 24 hours |