A Study of LY3127760 in Healthy Participants

Phase 1

Completed

Brief Summary: The main purposes of this study are to evaluate the safety and how well the body handles single and multiple doses of increasing strength of study drug, LY3127760. This study includes three parts. Part 3 may be initiated at sponsor's discretion, based on data from Part 2. Participants will only enroll in 1 of the 3 study parts. This study will last approximately 7 to 13 weeks, depending on part. Screening must be completed within 28 days prior to enrollment.

Recruitment & Eligibility

Inclusion Criteria

Overtly healthy males or females as determined by medical history and physical examination
Male participants agree to use a reliable method of birth control during the study and 3 months following the last dose of the investigational product
Female participants not of child-bearing potential
Have a body mass index of 18.5 to 32 kilograms per square meter (kg/m^2) inclusive
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 use of any antihypertensives

Exclusion Criteria

Have known allergies to LY3127760, related compounds or any components of the formulation, celecoxib or sulfonamides, or history of significant atopy. Participants with known aspirin allergy or allergic reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) should also be excluded
Have any current or prior history of a significant gastrointestinal illness such as peptic ulcer disease, gastrointestinal (GI) bleeding, chronic gastritis, inflammatory bowel disease or chronic diarrhea
Have evidence of other chronic liver disease, including but not limited to chronic alcoholic disease, nonalcoholic steatohepatitis, recent history (within 3 months of screening) of acute viral hepatitis or chronic autoimmune hepatitis
Have used any NSAIDs, celecoxib, aspirin or acetaminophen (at doses greater than 1 gram per day), anticoagulants or antiplatelet agents within 14 days of admission

Part 2 and Part 3 only

Arm && Interventions

Group	Intervention	Description
LY3127760 (Multiple)	LY3127760	Multiple ascending oral doses of up to 900 mg LY3127760 administered once or twice daily (QD or BID) for 28 days.
LY3127760 (Single)	LY3127760	Single oral dose of up to 900 milligram (mg) LY3127760 administered in up to 3 of 3 study periods.
Placebo (Single)	LY3127760	Single oral dose of placebo administered in up to 2 of 3 study periods. Placebo matches LY3127760 in appearance.
LY3127760 (Single)	Placebo	Single oral dose of up to 900 milligram (mg) LY3127760 administered in up to 3 of 3 study periods.
Placebo (Multiple)	LY3127760	Multiple oral doses of placebo administered QD or BID for 28 days. Placebo matches LY3127760 in appearance.
Placebo (Single)	Placebo	Single oral dose of placebo administered in up to 2 of 3 study periods. Placebo matches LY3127760 in appearance.
LY3127760 (Multiple)	Placebo	Multiple ascending oral doses of up to 900 mg LY3127760 administered once or twice daily (QD or BID) for 28 days.
Placebo (Multiple)	Placebo	Multiple oral doses of placebo administered QD or BID for 28 days. Placebo matches LY3127760 in appearance.
Celecoxib (Multiple)	Placebo	Multiple oral doses of 400 mg celecoxib administered QD for 28 days.
Celecoxib (Multiple)	LY3127760	Multiple oral doses of 400 mg celecoxib administered QD for 28 days.
Celecoxib (Multiple)	Celecoxib	Multiple oral doses of 400 mg celecoxib administered QD for 28 days.

Primary Outcome Measures

Name	Time	Method
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration	Baseline to Study Completion (Up To Day 42)	Data presented are the number of participants who experienced SAEs considered by the investigator to be related to study drug administration. A summary of SAEs and all other non-serious Adverse Event(s) (AEs), regardless of causality, is located in the Reported Adverse Event module.

Secondary Outcome Measures

Name	Time	Method
PK: Time of Maximum Observed Concentration (Tmax) of Single Dose LY3127760	Day 1: -1, 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 96, and 144 Hours
PK: Area Under the Concentration Versus Time Curve During One Dosing Interval [AUC-tau (τ)] of Multiple Doses LY3127760	Day 28: -1, 0.25, 0.5, 1, 2, 4, 8, 12, 16, and 24 Hours	AUC-tau (τ) where τ is 24-hours for the 20 mg, 60 mg, and 200 mg cohorts, and 12-hours for the 300 mg cohort.
Pharmacokinetics (PK): Area Under the Concentration Curve Versus Time Curve From Zero to Infinity (AUC 0-∞) of Single Dose LY3127760	Day 1: -1, 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 96, and 144 Hours
PK: Maximum Observed Concentration (Cmax) of Single Dose LY3127760	Day 1: -1, 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 36, 48, 96, and 144 Hours
PK: Tmax of Multiple Doses LY3127760	Post-last dose on Day 28: 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 72, and 168 Hours
PK: Cmax of Multiple Doses LY3127760	Post last dose on Day 28: 0.25, 0.5, 1, 2, 4, 8, 12, 16, 24, 72, and 168 Hours

Locations (1): For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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Evansville, Indiana, United States