A Single Dose Study of LY3023703 in Healthy Participants

Study Overview
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Brief Summary
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This is a phase I study of LY3023703 in healthy participants. The purposes of this study are to look at safety, how well the study drug is tolerated, how much of the study drug gets into the blood stream, and how long it takes the body to get rid of it when given to humans. Information about any side effects that may occur will also be collected. Participants will remain in the study for approximately 3 months. This study is for research purposes only and is not intended to treat any medical condition.

Official Title
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A Single-Dose, Dose-Escalation Study to Evaluate the Safety and Tolerability of LY3023703 in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: LY3023703
* Drug: Placebo
* Drug: Celecoxib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overtly healthy individuals based on the history and physical examinations as determined by the investigator Body mass index between 18.5 and 32.0 kilograms per square meter (kg/m^2), inclusive Exclusion Criteria: Have known allergies to LY3023703 or any components of the formulation, celecoxib, or sulfonamides. Participants with known aspirin allergy, allergic reaction to nonsteroidal anti-inflammatory drugs (NSAIDs), or allergies or intolerance to other selective microsomal prostaglandin E synthase (mPGES-1) inhibitors should also be excluded Have the presence of active peptic ulcer disease, gastrointestinal (GI) bleeding, chronic gastritis, inflammatory bowel disease, or chronic diarrhea, or positive Helicobacter pylori serology Use NSAIDs, celecoxib, aspirin, or acetaminophen (at doses greater than 1 gram per day) within 14 days of screening

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Single dose of placebo administered orally on up to one occasion separated by at least a 3 week wash out period. | Drug: Placebo<br>* Administered orally<br>|
| Experimental: LY3023703<br>Up to 6 single escalating doses of LY3023703 [0.1 milligram (mg) up to 60 mg] administered orally on up to two occasions per participant separated by at least a 3 week wash out period. | Drug: LY3023703<br>* Administered orally<br>|
| Active Comparator: 400 mg Celecoxib<br>Positive control. Single 400 mg dose of celecoxib administered orally, open label, on one occasion separated by at least a 3 week washout period. | Drug: Celecoxib<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 One or More Drug Related Adverse Events (AEs) or Any Serious AE | AEs that were considered possibly related to study drug, in the opinion of the investigator, were reported. A summary of serious and all other non-serious AEs, regardless of possible study drug relatedness, is located in the Reported Adverse Events module. | Baseline up to Day 7 post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 |  | Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 8 and 12 hours, post-dose | 
| Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3023703 | Area under the concentration time curve from the time of dosing to the time of the last observation. | Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 8 and 12 hours, post-dose | 
| Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent change from baseline of PGE synthesis=(postdose PGE synthesis-baseline PGE synthesis)/baseline PGE synthesis*100, where the unit of measure for PGE synthesis is nanograms per milliliter (ng/ml). | Baseline, 0.5 hours (h), 1 h, 2 h, 8 h, 24 h, and 144 h post-dose | 
| Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Urinary excretion of PGEM, after correcting for urinary creatinine. PGEM was corrected for urinary creatinine by dividing the picograms per milliliter (pg/mL) of metabolite excreted in urine by the concentration of creatinine [milligrams per milliliter (mg/mL)] in urine. Percent change from baseline of urinary excretion of PGEM=(mg creatinine per pg of metabolite excreted in urine postdose-mg of creatinine per pg of metabolite excreted at baseline)/mg of creatinine per pg of metabolite excreted at baseline*100. | Baseline, 0 to 2 hours (h), 2 to 4 h, 4 to 6 h, 6 to 12 h, and 12 to 24 hours post-dose | 
| Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Urinary excretion of PGIM, after correcting for urinary creatinine. PGIM was corrected for urinary creatinine by dividing the picograms per milliliter (pg/mL) of metabolite excreted in urine by the concentration of creatinine [milligrams per milliliter (mg/mL)] in urine. Percent change from baseline of urinary excretion of PGIM=(mg creatinine per pg of metabolite excreted in urine postdose-mg of creatinine per pg of metabolite excreted at baseline)/mg of creatinine per pg of metabolite excreted at baseline*100. | Baseline, 0 to 2 hours (h), 2 to 4 h, 4 to 6 h, and 6 to 12 h post-dose | 
| Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Urinary excretion of TXAM, after correcting for urinary creatinine. TXAM was corrected for urinary creatinine by dividing the picograms per milliliter (pg/mL) of metabolite excreted in urine by the concentration of creatinine [milligrams per milliliter (mg/mL)] in urine. Percent change from baseline of urinary excretion of TXAM=(mg creatinine per pg of metabolite excreted in urine postdose-mg of creatinine per pg of metabolite excreted at baseline)/mg of creatinine per pg of metabolite excreted at baseline*100. | Baseline, 0 to 2 hours (h), 2 to 4 h, 4 to 6 h, and 6 to 12 h post-dose |