A Multiple Dose Study of LY3023703 in Healthy Participants

Study Overview
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Brief Summary
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This is a 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 remove the study drug. The effects of LY3023703 on blood pressure after 28 days of dosing will be studied. Information about any side effects that occur will be collected. The study is expected to last 21 weeks.

Official Title
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A Multiple-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: Placebo
* Drug: LY3023703
* 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 Are normotensive (defined as supine systolic blood pressure [BP] less than 140 millimeters of mercury [mm Hg] and diastolic BP less than 90 mm Hg without the use of any antihypertensives) or results that are judged to be not clinically significant by the investigator Exclusion Criteria: Have presence of clinically significant active bleeding or history of bleeding diathesis at the time of screening Have presence of active peptic ulcer disease, gastro-intestinal (GI) bleeding, chronic gastritis, inflammatory bowel disease, or chronic diarrhea Have evidence of other chronic liver disease Have any use of nonsteroidal anti-inflammatory drugs (NSAIDs), celecoxib, aspirin, or acetaminophen (at doses greater than 1 gram per day [g/day] within 14 days of admission Have greater than 1 plus pretibial pitting edema or 2 plus ankle or pedal edema

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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo matching LY3023703 administered orally, once daily (QD), for 28 days | Drug: Placebo<br>* Administered orally<br>|
| Experimental: LY3023703<br>Escalating doses (2.5 milligram [mg] up to 30 mg) of LY3023703 administered orally, QD, for 28 days | Drug: LY3023703<br>* Administered orally<br>|
| Active Comparator: Celecoxib<br>400 mg celecoxib administered orally, QD, for 28 days. (Positive control.) | 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 Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | A summary of serious and all other non-serious adverse events (AE), regardless of possible study drug relatedness, is located in the Reported Adverse Events module. | Baseline to Study Completion (up to 74 Days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve [AUC(0-24)] of LY3023703 |  | Post-First Dose on Days 1-28 (Time Frame: Day 1: -0.5, 1, 2, 4, 8, 12, 24 hours; Days 5, 12, 20: -0.5 hours; Day 28: -0.5, 1, 2, 4, 8, 12, 24 hours.) | 
| Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 |  | Post first dose on Day 1 through Day 28 (Time Frame: Day 1: -0.5, 1, 2, 4, 8, 12, 24 hours; Days 5, 12, 20: -0.5 hours; Day 28: -0.5, 1, 2, 4, 8, 12, 24 hours.) | 
| Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3023703 |  | Post first dose on Day 1 through Day 28 (Time Frame: Day 1: -0.5, 1, 2, 4, 8, 12, 24 hours; Days 5, 12, 20: -0.5 hours; Day 28: -0.5, 1, 2, 4, 8, 12, 24 hours.) | 
| Change From Baseline to Day 27 in Blood Pressure (BP) | The Day 27 change from Day -1 was analyzed by using analysis of covariance (ANCOVA) with treatment as a fixed effect and baseline Day -1 as a covariate. The treatment mean, difference to placebo, and difference to celecoxib were output with corresponding 90% confidence intervals. | Baseline, Day 27 |