A Single-Dose, Dose-Escalation Study to Evaluate the Safety and Tolerability of LY3023703 in Healthy Subjects
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Eli Lilly and Company
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE
Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 60 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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
Arms & Interventions
Placebo
Single dose of placebo administered orally on up to one occasion separated by at least a 3 week wash out period.
Intervention: Placebo (Drug)
LY3023703
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.
Intervention: LY3023703 (Drug)
400 mg Celecoxib
Positive control. Single 400 mg dose of celecoxib administered orally, open label, on one occasion separated by at least a 3 week washout period.
Intervention: Celecoxib (Drug)
Outcomes
Primary Outcomes
Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE
Time Frame: Baseline up to Day 7 post-dose
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.
Secondary Outcomes
- Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703(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(Baseline, 0.5 hours (h), 1 h, 2 h, 8 h, 24 h, and 144 h post-dose)
- Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3023703(Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 8 and 12 hours, post-dose)
- Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM)(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)(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)(Baseline, 0 to 2 hours (h), 2 to 4 h, 4 to 6 h, and 6 to 12 h post-dose)