Healthy Volunteers
Conditions
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.
Interventions
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | Area under the concentration time curve from the time of dosing to the time of the last observation. |
| 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 | 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). |
| 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 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 | 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. |
| 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 | 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. |
| 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 | 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. |
Countries
United States
Participant flow
Pre-assignment details
The study had 3 periods. Period 1: 0.1 milligram (mg), 0.5 mg, 2.5 mg LY3023703 or placebo. Period 2: 10 mg, 30 mg, 60 mg LY3023703 or placebo. Period 3: 400 mg celecoxib. There was at least a 3-week washout between periods and at least 7 days between dosing of each cohort in Periods 1 and 2.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Depending on the cohort and period, participants received either an LY3023703 capsule (0.1-mg, 0.5-mg, 2.5-mg, 10-mg, 30-mg, or 60-mg strength) or placebo administered orally once in Periods 1 and 2. In Period 3, participants were administered 400 mg celecoxib, orally. Each dose of study drug was followed by a washout period of at least 3 weeks. | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Period 2 (Second Intervention) | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Washout Period | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 47.0 years STANDARD_DEVIATION 10.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Region of Enrollment United States | 30 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 12 | 1 / 8 | 0 / 8 | 2 / 8 | 0 / 7 | 4 / 8 | 2 / 8 | 2 / 28 |
| serious Total, serious adverse events | 0 / 12 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 7 | 0 / 8 | 0 / 8 | 0 / 28 |
Outcome results
Primary
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.
Time frame: Baseline up to Day 7 post-dose
Population: Safety population: participants who received at least 1 dose of study drug or placebo, whether or not he/she completed all the protocol requirements.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | Drug-Related AE | 3 Participants |
| Placebo | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | Any Serious AE | 0 Participants |
| 0.1 mg LY3023703 | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | Drug-Related AE | 0 Participants |
| 0.1 mg LY3023703 | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | Any Serious AE | 0 Participants |
| 0.5 mg LY3023703 | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | Drug-Related AE | 0 Participants |
| 0.5 mg LY3023703 | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | Any Serious AE | 0 Participants |
| 2.5 mg LY3023703 | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | Drug-Related AE | 0 Participants |
| 2.5 mg LY3023703 | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | Any Serious AE | 0 Participants |
| 10 mg LY3023703 | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | Any Serious AE | 0 Participants |
| 10 mg LY3023703 | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | Drug-Related AE | 0 Participants |
| 30 mg LY3023703 | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | Any Serious AE | 0 Participants |
| 30 mg LY3023703 | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | Drug-Related AE | 0 Participants |
| 60 mg LY3023703 | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | Any Serious AE | 0 Participants |
| 60 mg LY3023703 | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | Drug-Related AE | 1 Participants |
| Celecoxib | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | Drug-Related AE | 1 Participants |
| Celecoxib | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE | Any Serious AE | 0 Participants |
Secondary
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).
Time frame: Baseline, 0.5 hours (h), 1 h, 2 h, 8 h, 24 h, and 144 h post-dose
Population: All participants who received at least 1 dose of study drug or placebo and had evaluable PGE data at the specific time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 1 h | 25.4 percent change in PGE |
| Placebo | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 8 h | 30.0 percent change in PGE |
| Placebo | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 24 h | -29.0 percent change in PGE |
| Placebo | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 2 h | 11.2 percent change in PGE |
| Placebo | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 0.5 h | -10.1 percent change in PGE |
| Placebo | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 144 h | -36.8 percent change in PGE |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 1 h | 106.4 percent change in PGE |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 144 h | -31.1 percent change in PGE |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 2 h | 87.9 percent change in PGE |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 0.5 h | 102.6 percent change in PGE |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 8 h | 44.2 percent change in PGE |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 8 h | 90.5 percent change in PGE |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 0.5 h | -11.6 percent change in PGE |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 1 h | -6.2 percent change in PGE |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 144 h | 20.5 percent change in PGE |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 2 h | 52.1 percent change in PGE |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 24 h | 44.1 percent change in PGE |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 0.5 h | 29.3 percent change in PGE |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 2 h | -59.6 percent change in PGE |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 144 h | 28.9 percent change in PGE |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 24 h | -7.6 percent change in PGE |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 1 h | -18.9 percent change in PGE |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 8 h | 3.3 percent change in PGE |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 2 h | -82.7 percent change in PGE |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 24 h | 16.1 percent change in PGE |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 0.5 h | -12.1 percent change in PGE |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 144 h | 111.6 percent change in PGE |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 8 h | -56.0 percent change in PGE |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 1 h | -67.6 percent change in PGE |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 144 h | -61.3 percent change in PGE |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 0.5 h | -43.5 percent change in PGE |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 1 h | -84.1 percent change in PGE |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 2 h | -102.0 percent change in PGE |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 8 h | -96.5 percent change in PGE |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 24 h | -84.2 percent change in PGE |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 2 h | -89.1 percent change in PGE |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 1 h | -82.4 percent change in PGE |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 24 h | -80.7 percent change in PGE |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 0.5 h | -27.1 percent change in PGE |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 144 h | 4.3 percent change in PGE |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 8 h | -96.1 percent change in PGE |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 8 h | -26.7 percent change in PGE |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 2 h | -42.5 percent change in PGE |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 1 h | -14.0 percent change in PGE |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 144 h | 11.6 percent change in PGE |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 24 h | -21.8 percent change in PGE |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Percent Change at 0.5 h | -7.1 percent change in PGE |
Secondary
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.
Time frame: Baseline, 0 to 2 hours (h), 2 to 4 h, 4 to 6 h, and 6 to 12 h post-dose
Population: All participants who received at least 1 dose of study drug or placebo and had evaluable PGIM data at specific time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 0 to 2 h | -6.4 percent change in PGIM |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 4 to 6 h | -0.9 percent change in PGIM |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 6 to 12 h | -6.1 percent change in PGIM |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 2 to 4 h | -10.9 percent change in PGIM |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 6 to 12 h | -29.8 percent change in PGIM |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 0 to 2 h | -34.6 percent change in PGIM |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 4 to 6 h | -19.1 percent change in PGIM |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 2 to 4 h | -19.6 percent change in PGIM |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 4 to 6 h | -3.5 percent change in PGIM |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 2 to 4 h | 18.6 percent change in PGIM |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 6 to 12 h | 13.6 percent change in PGIM |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 0 to 2 h | 15.5 percent change in PGIM |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 0 to 2 h | 22.4 percent change in PGIM |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 4 to 6 h | 3.7 percent change in PGIM |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 6 to 12 h | 0.6 percent change in PGIM |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 2 to 4 h | 9.8 percent change in PGIM |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 0 to 2 h | -1.2 percent change in PGIM |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 4 to 6 h | -0.9 percent change in PGIM |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 2 to 4 h | 29.3 percent change in PGIM |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 6 to 12 h | 98.4 percent change in PGIM |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 2 to 4 h | 51.5 percent change in PGIM |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 0 to 2 h | 33.1 percent change in PGIM |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 4 to 6 h | 19.5 percent change in PGIM |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 6 to 12 h | 44.1 percent change in PGIM |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 2 to 4 h | 74.5 percent change in PGIM |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 4 to 6 h | 63.3 percent change in PGIM |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 0 to 2 h | 27.7 percent change in PGIM |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 6 to 12 h | 49.9 percent change in PGIM |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 6 to 12 h | -45.2 percent change in PGIM |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 4 to 6 h | -60.0 percent change in PGIM |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 0 to 2 h | -32.0 percent change in PGIM |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | Percent Change at 2 to 4 h | -66.0 percent change in PGIM |
Secondary
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.
Time frame: 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
Population: All participants who received at least 1 dose of study drug or placebo and had evaluable PGEM data at specific time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 2 to 4 h | -2.8 percent change in PGEM |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 0 to 2 h | 4.2 percent change in PGEM |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 12 to 24 h | -29.7 percent change in PGEM |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 4 to 6 h | -19.0 percent change in PGEM |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 6 to 12 h | -18.7 percent change in PGEM |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 4 to 6 h | -0.0 percent change in PGEM |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 2 to 4 h | 0.7 percent change in PGEM |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 6 to 12 h | -18.5 percent change in PGEM |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 12 to 24 h | -38.8 percent change in PGEM |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 0 to 2 h | 7.4 percent change in PGEM |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 0 to 2 h | -4.0 percent change in PGEM |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 12 to 24 h | -18.0 percent change in PGEM |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 6 to 12 h | 2.3 percent change in PGEM |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 2 to 4 h | 7.9 percent change in PGEM |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 4 to 6 h | -25.0 percent change in PGEM |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 4 to 6 h | -19.0 percent change in PGEM |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 0 to 2 h | 1.5 percent change in PGEM |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 2 to 4 h | -0.8 percent change in PGEM |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 6 to 12 h | -20.4 percent change in PGEM |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 12 to 24 h | -19.1 percent change in PGEM |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 6 to 12 h | -39.5 percent change in PGEM |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 0 to 2 h | -5.3 percent change in PGEM |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 4 to 6 h | -29.1 percent change in PGEM |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 2 to 4 h | -21.0 percent change in PGEM |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 12 to 24 h | -28.8 percent change in PGEM |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 2 to 4 h | -46.6 percent change in PGEM |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 4 to 6 h | -53.0 percent change in PGEM |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 0 to 2 h | 17.7 percent change in PGEM |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 6 to 12 h | -37.5 percent change in PGEM |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 12 to 24 h | -31.2 percent change in PGEM |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 0 to 2 h | -6.6 percent change in PGEM |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 2 to 4 h | -25.1 percent change in PGEM |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 4 to 6 h | -42.4 percent change in PGEM |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 12 to 24 h | -53.0 percent change in PGEM |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 6 to 12 h | -48.0 percent change in PGEM |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 2 to 4 h | -41.5 percent change in PGEM |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 6 to 12 h | -49.7 percent change in PGEM |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 0 to 2 h | -7.5 percent change in PGEM |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 12 to 24 h | -46.2 percent change in PGEM |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | Percent Change at 4 to 6 h | -55.0 percent change in PGEM |
Secondary
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.
Time frame: Baseline, 0 to 2 hours (h), 2 to 4 h, 4 to 6 h, and 6 to 12 h post-dose
Population: All participants who received at least 1 dose of study drug or placebo and had evaluable TXAM data at specific time points.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 6 to 12 h | -8.7 percent change in TXAM |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 0 to 2 h | -9.1 percent change in TXAM |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 4 to 6 h | -15.0 percent change in TXAM |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 2 to 4 h | -12.5 percent change in TXAM |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 2 to 4 h | -11.5 percent change in TXAM |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 6 to 12 h | -13.8 percent change in TXAM |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 0 to 2 h | -19.9 percent change in TXAM |
| 0.1 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 4 to 6 h | -19.8 percent change in TXAM |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 6 to 12 h | 7.7 percent change in TXAM |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 2 to 4 h | 11.1 percent change in TXAM |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 0 to 2 h | 6.5 percent change in TXAM |
| 0.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 4 to 6 h | 2.6 percent change in TXAM |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 6 to 12 h | -19.2 percent change in TXAM |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 4 to 6 h | -18.8 percent change in TXAM |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 2 to 4 h | -7.9 percent change in TXAM |
| 2.5 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 0 to 2 h | -17.9 percent change in TXAM |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 4 to 6 h | 16.4 percent change in TXAM |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 2 to 4 h | 21.4 percent change in TXAM |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 6 to 12 h | 18.0 percent change in TXAM |
| 10 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 0 to 2 h | 8.7 percent change in TXAM |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 6 to 12 h | 9.8 percent change in TXAM |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 0 to 2 h | 2.7 percent change in TXAM |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 4 to 6 h | -13.1 percent change in TXAM |
| 30 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 2 to 4 h | 26.3 percent change in TXAM |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 2 to 4 h | 13.0 percent change in TXAM |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 4 to 6 h | 18.5 percent change in TXAM |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 0 to 2 h | -10.2 percent change in TXAM |
| 60 mg LY3023703 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 6 to 12 h | 19.1 percent change in TXAM |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 2 to 4 h | -17.7 percent change in TXAM |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 0 to 2 h | -5.0 percent change in TXAM |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 6 to 12 h | -16.2 percent change in TXAM |
| Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | Percent Change at 4 to 6 h | -25.7 percent change in TXAM |
Secondary
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.
Time frame: Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 8 and 12 hours, post-dose
Population: Pharmacokinetic (PK) population: All participants who received at least 1 dose of study drug and had evaluable AUC data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3023703 | 3.19 hour*nanograms per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 52 |
| 0.1 mg LY3023703 | Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3023703 | 54.7 hour*nanograms per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 72.4 |
| 0.5 mg LY3023703 | Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3023703 | 245 hour*nanograms per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 58.5 |
| 2.5 mg LY3023703 | Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3023703 | 1680 hour*nanograms per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 36.8 |
| 10 mg LY3023703 | Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3023703 | 9940 hour*nanograms per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 45.6 |
| 30 mg LY3023703 | Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3023703 | 13800 hour*nanograms per milliliter (hr*ng/mL) | Geometric Coefficient of Variation 30 |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703
Time frame: Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 8 and 12 hours, post-dose
Population: Pharmacokinetic (PK) population: participants who received at least 1 dose of study drug and had evaluable Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 | 1.15 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 25.4 |
| 0.1 mg LY3023703 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 | 5.66 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 27.7 |
| 0.5 mg LY3023703 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 | 23.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 23.7 |
| 2.5 mg LY3023703 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 | 140 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 22 |
| 10 mg LY3023703 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 | 547 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 36 |
| 30 mg LY3023703 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 | 756 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 26.8 |