A Multiple-dose Study of LY3031207 in Healthy Participants

Study Overview
=================
Brief Summary
-----------------
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 healthy Japanese and non-Japanese participants as multiple doses. In addition, effects of 28-day oral dosing of LY3031207 on the amount of a cholesterol-lowering drug (simvastatin) that gets into the blood stream and how long the body takes to get rid of it will be determined. The effects of LY3031207 after single and 28-day dosing on blood pressure will also be studied. Information about any side effects that may occur will be collected.

Official Title
-----------------
A Multiple-Dose, Dose-Escalation Study to Evaluate the Safety and Tolerability of LY3031207 in Healthy Subjects

Conditions
-----------------
Healthy Volunteers

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: LY3031207
* Drug: Celecoxib
* Drug: Simvastatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Overtly healthy individuals based on the history and physical examinations as determined by the investigator, including first generation Japanese Body mass index between 17.0 and 32.0 kilograms per square meter (kg/m^2), inclusive Exclusion Criteria: Have known allergies to LY3031207 or any components of the formulation, simvastatin or related compounds (other 3-Hydroxy-3-Methyl-Glutaryl-CoA [HMG CoA] reductase inhibitors), celecoxib, or sulfonamides. Participants with known aspirin allergy or allergic reaction to nonsteroidal anti-inflammatory drugs (NSAIDs) should also be excluded

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

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>Daily oral administration of placebo for 28 days. Dose will match corresponding LY3031207 dosage. | Drug: Placebo<br>* Capsules administered orally<br>|
| Experimental: LY3031207<br>Daily oral administration of 25 milligrams (mg) LY3031207 up to 450 mg LY3031207 for 28 days. | Drug: LY3031207<br>* Administered orally<br>|
| Active Comparator: Celecoxib<br>Daily oral administration of 400 mg celecoxib for 28 days. Positive control for LY3031207. | Drug: Celecoxib<br>* Administered orally<br>|
| Other: LY3031207 + Simvastatin<br>Daily oral administration of 75 mg LY3031207 or 225 mg LY3031207 for 28 days. Single, oral 10 mg simvastatin open-label dose administered before and after 28-day dosing of LY3031207. | Drug: Simvastatin<br>* Administered orally<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs | A treatment emergent adverse event (TEAE) is defined as an adverse event (AE) that occurs postdose or that is present predose and becomes more severe postdose. AEs presented are of all causalities and all severities. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. | Baseline to study completion (treatment completion and follow-up, up to 35 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207 | Maximum concentration (Cmax) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm. | Predose up to 48 hours post last dose at Day 28 | 
| Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3031207 | Area under the concentration versus time curve in a dosing interval (AUC[0-tau]) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm. | Predose up to 48 hours post last dose at Day 28 | 
| Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3031207 | Time of maximum concentration (Tmax) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm. | Predose up to 48 hours post last dose at Day 28 | 
| Pharmacokinetics: Maximum Concentration (Cmax) of Simvastatin |  | Predose up to 48 hours post dose at Day -3 and Day 28 | 
| Pharmacokinetics: Area Under the Concentration Curve (AUC) of Simvastatin | Area under the concentration versus time curve over the range of all measureable concentrations (AUC[0-tlast]) of simvastatin. | Predose up to 48 hours post dose at Day -3 and Day 28 | 
| Pharmacokinetics: Time of Maximum Concentration (Tmax) of Simvastatin |  | Predose up to 48 hours post dose at Day -3 and Day 28 | 
| Change From Baseline to Day 28 in Urinary Prostacyclin I (PGI) Metabolite Excretion |  | Baseline, Predose up to 12 hours prior to last dose at Day 28 | 
| Change From Baseline to Day 28 in Urinary Prostaglandin E (PGE) Metabolite Excretion |  | Baseline, Predose up to time of last dose at Day 28 | 
| Change From Baseline to Day 28 in Urinary Thromboxane A (TXA) Metabolite Excretion |  | Baseline, Predose up to 12 hours prior to last dose at Day 28 |