A Single Dose Study of LY3023703 in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01632579
• Collaborator: (none)
• Enrollment: 30
• Location: 1
• Arms: 3
• Duration (Months): 3
• Patients Per Site Per Month: 9.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: LY3023703; Drug: Placebo; Drug: Celecoxib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Basic Science
• Official Title: A Single-Dose, Dose-Escalation Study to Evaluate the Safety and Tolerability of LY3023703 in Healthy Subjects
• Study Start Date: Jun 1, 2012
• Actual Primary Completion Date: Sep 1, 2012
• Actual Study Completion Date: Sep 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Single dose of placebo administered orally on up to one occasion separated by at least a 3 week wash out period.	Drug: Placebo; Administered orally
Experimental: 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.	Drug: LY3023703; Administered orally
Active Comparator: 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.	Drug: Celecoxib; Administered orally

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 [Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 8 and 12 hours, post-dose]

2. 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.

3. 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).

4. 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.

5. 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.

6. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
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.	Evansville	Indiana	United States

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri, 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01632579
• Other Study ID Numbers: 14707; I6H-MC-MCBA
• First Posted: Jul 3, 2012
• Last Update Posted: Aug 6, 2018
• Last Verified: Jul 1, 2018

• Additional relevant MeSH terms: Celecoxib

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Cohort 1 Sequence 1	Cohort 1 Sequence 2	Cohort 1 Sequence 3	Cohort 2 Sequence 1	Cohort 2 Sequence 2	Cohort 2 Sequence 3	Cohort 3 Sequence 1	Cohort 3 Sequence 2	Cohort 3 Sequence 3
Arm/Group Description	Participants received LY3023703, placebo and celecoxib capsules orally as per the below dosing sequence in each period. Period 1: 0.1 mg LY3023703 in week 1, Period 2: Placebo in week 4 and Period 3: 400mg celecoxib in week 8.	Participants received LY3023703 and celecoxib capsules orally as per the below dosing sequence in each period. Period 1: 0.1 mg LY3023703 in week 1, Period 2: 10 mg LY3023703 in week 4 and Period 3: 400mg celecoxib in week 7.	Participants received placebo, LY3023703 and celecoxib capsules orally as per the below dosing sequence in each period. Period 1: Placebo in week 1, Period 2: 10 mg LY3023703 in week 4 and Period 3: 400mg celecoxib in week 7.	Participants received LY3023703, placebo and celecoxib capsules orally as per the below dosing sequence in each period. Period 1: 0.5 mg LY3023703 in week 2, Period 2: Placebo in week 5 and Period 3: 400mg celecoxib in week 8.	Participants received LY3023703 and celecoxib capsules orally as per the below dosing sequence in each period. Period 1: 0.5 mg LY3023703 in week 2, Period 2: 30 mg LY3023703 in week 5 and Period 3: 400mg celecoxib in week 8.	Participants received placebo, LY3023703 and celecoxib capsules orally as per the below dosing sequence in each period. Period 1: Placebo in week 2, Period 2: 30 mg LY3023703 in week 5 and Period 3: 400mg celecoxib in week 8.	Participants received LY3023703, placebo and celecoxib capsules orally as per the below dosing sequence in each period. Period 1: 2.5 mg LY3023703 in week 3, Period 2: Placebo in week 6 and Period 3: 400mg celecoxib in week 9.	Participants received LY3023703 and celecoxib capsules orally as per the below dosing sequence in each period. Period 1: 2.5 mg LY3023703 in week 3, Period 2: 60 mg LY3023703 in week 6 and Period 3: 400mg celecoxib in week 9.	Participants received placebo, LY3023703 and celecoxib capsules orally as per the below dosing sequence in each period. Period 1: Placebo in week 3, Period 2: 60 mg LY3023703 in week 6 and Period 3: 400mg celecoxib in week 9.
Period Title: Period 1 (First Intervention)
STARTED	2	6	2	2	6	2	2	6	2
Received at Least 1 Dose	2	6	2	2	6	2	2	6	2
COMPLETED	2	6	2	2	6	2	2	6	2
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Period 1 (First Intervention)
STARTED	2	6	2	2	6	2	2	6	2
COMPLETED	1	6	2	2	6	2	2	6	2
NOT COMPLETED	1	0	0	0	0	0	0	0	0
Period Title: Period 1 (First Intervention)
STARTED	1	6	2	2	6	2	2	6	2
Received at Least 1 Dose	1	6	2	2	6	2	2	6	2
COMPLETED	0	6	2	2	6	2	2	6	2
NOT COMPLETED	1	0	0	0	0	0	0	0	0
Period Title: Period 1 (First Intervention)
STARTED	0	6	2	2	6	2	2	6	2
COMPLETED	0	6	2	2	6	2	2	6	2
NOT COMPLETED	0	0	0	0	0	0	0	0	0
Period Title: Period 1 (First Intervention)
STARTED	0	6	2	2	6	2	2	6	2
Received at Least 1 Dose	0	6	2	2	6	2	2	6	2
COMPLETED	0	6	2	2	6	2	2	6	2
NOT COMPLETED	0	0	0	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	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.
Overall Participants	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.0 (10.9)
Sex: Female, Male (Count of Participants)
Female	11 36.7%
Male	19 63.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 3.3%
Not Hispanic or Latino	29 96.7%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 3.3%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 10%
White	26 86.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	30 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo	0.1 mg LY3023703	0.5 mg LY3023703	2.5 mg LY3023703	10 mg LY3023703	30 mg LY3023703	60 mg LY3023703	Celecoxib
Arm/Group Description	Matched placebo capsules administered orally in Periods 1 or 2.	0.1-milligram (mg) LY3023703 capsule administered orally, once in Period 1.	0.5-mg LY3023703 capsule administered orally, once in Period 1.	2.5-mg LY3023703 capsule administered orally, once in Period 1.	10-mg LY3023703 capsule administered orally, once in Period 2.	30-mg LY3023703 capsule administered orally, once in Period 2.	60-mg LY3023703 capsule administered orally, once in Period 2.	400-mg celecoxib dose (two 200-mg celecoxib capsules) administered orally, once in Period 3.
Measure Participants	12	8	8	8	7	8	8	28
Any Serious AE	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Drug-Related AE	3 10%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	1 NaN	1 NaN

2. Secondary Outcome

Title	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population: participants who received at least 1 dose of study drug and had evaluable Cmax data.

Arm/Group Title	0.1 mg LY3023703	0.5 mg LY3023703	2.5 mg LY3023703	10 mg LY3023703	30 mg LY3023703	60 mg LY3023703
Arm/Group Description	0.1-milligram (mg) LY3023703 capsule administered orally, once in Period 1.	0.5-mg LY3023703 capsule administered orally, once in Period 1.	2.5-mg LY3023703 capsule administered orally, once in Period 1.	10-mg LY3023703 capsule administered orally, once in Period 2.	30-mg LY3023703 capsule administered orally, once in Period 2.	60-mg LY3023703 capsule administered orally, once in Period 2.
Measure Participants	8	8	8	7	8	8
Geometric Mean (Geometric Coefficient of Variation) [nanograms per milliliter (ng/mL)]	1.15 (25.4)	5.66 (27.7)	23.5 (23.7)	140 (22.0)	547 (36.0)	756 (26.8)

3. Secondary Outcome

Title	Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3023703
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) population: All participants who received at least 1 dose of study drug and had evaluable AUC data.

Arm/Group Title	0.1 mg LY3023703	0.5 mg LY3023703	2.5 mg LY3023703	10 mg LY3023703	30 mg LY3023703	60 mg LY3023703
Arm/Group Description	0.1-milligram (mg) LY3023703 capsule administered orally, once in Period 1.	0.5-mg LY3023703 capsule administered orally, once in Period 1.	2.5-mg LY3023703 capsule administered orally, once in Period 1.	10-mg LY3023703 capsule administered orally, once in Period 2.	30-mg LY3023703 capsule administered orally, once in Period 2.	60-mg LY3023703 capsule administered orally, once in Period 2.
Measure Participants	8	8	8	7	8	8
Geometric Mean (Geometric Coefficient of Variation) [hour*nanograms per milliliter (hr*ng/mL)]	3.19 (52.0)	54.7 (72.4)	245 (58.5)	1680 (36.8)	9940 (45.6)	13800 (30.0)

4. Secondary Outcome

Title	Pharmacodynamics: Percent Change From Baseline of ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation
Description	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

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug or placebo and had evaluable PGE data at the specific time points.

Arm/Group Title	Placebo	0.1 mg LY3023703	0.5 mg LY3023703	2.5 mg LY3023703	10 mg LY3023703	30 mg LY3023703	60 mg LY3023703	Celecoxib
Arm/Group Description	Matched placebo capsules administered orally in Periods 1 or 2.	0.1-milligram (mg) LY3023703 capsule administered orally, once in Period 1.	0.5-mg LY3023703 capsule administered orally, once in Period 1.	2.5-mg LY3023703 capsule administered orally, once in Period 1.	10-mg LY3023703 capsule administered orally, once in Period 2.	30-mg LY3023703 capsule administered orally, once in Period 2.	60-mg LY3023703 capsule administered orally, once in Period 2.	400-mg celecoxib dose (two 200-mg celecoxib capsules) administered orally, once in Period 3.
Measure Participants	11	1	8	8	7	8	8	28
Percent Change at 0.5 h	-10.1	102.6	-11.6	29.3	-12.1	-43.5	-27.1	-7.1
Percent Change at 1 h	25.4	106.4	-6.2	-18.9	-67.6	-84.1	-82.4	-14.0
Percent Change at 2 h	11.2	87.9	52.1	-59.6	-82.7	-102.0	-89.1	-42.5
Percent Change at 8 h	30.0	44.2	90.5	3.3	-56.0	-96.5	-96.1	-26.7
Percent Change at 24 h	-29.0	44.1	-7.6	16.1	-84.2	-80.7	-21.8
Percent Change at 144 h	-36.8	-31.1	20.5	28.9	111.6	-61.3	4.3	11.6

5. Secondary Outcome

Title	Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM)
Description	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

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug or placebo and had evaluable PGEM data at specific time points.

Arm/Group Title	Placebo	0.1 mg LY3023703	0.5 mg LY3023703	2.5 mg LY3023703	10 mg LY3023703	30 mg LY3023703	60 mg LY3023703	Celecoxib
Arm/Group Description	Matched placebo capsules administered orally in Periods 1 or 2.	0.1-milligram (mg) LY3023703 capsule administered orally, once in Period 1.	0.5-mg LY3023703 capsule administered orally, once in Period 1.	2.5-mg LY3023703 capsule administered orally, once in Period 1.	10-mg LY3023703 capsule administered orally, once in Period 2.	30-mg LY3023703 capsule administered orally, once in Period 2.	60-mg LY3023703 capsule administered orally, once in Period 2.	400-mg celecoxib dose (two 200-mg celecoxib capsules) administered orally, once in Period 3.
Measure Participants	12	8	8	8	7	8	7	27
Percent Change at 0 to 2 h	4.2	7.4	-4.0	1.5	-5.3	17.7	-6.6	-7.5
Percent Change at 2 to 4 h	-2.8	0.7	7.9	-0.8	-21.0	-46.6	-25.1	-41.5
Percent Change at 4 to 6 h	-19.0	-0.0	-25.0	-19.0	-29.1	-53.0	-42.4	-55.0
Percent Change at 6 to 12 h	-18.7	-18.5	2.3	-20.4	-39.5	-37.5	-48.0	-49.7
Percent Change at 12 to 24 h	-29.7	-38.8	-18.0	-19.1	-28.8	-31.2	-53.0	-46.2

6. Secondary Outcome

Title	Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM)
Description	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

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug or placebo and had evaluable PGIM data at specific time points.

Arm/Group Title	Placebo	0.1 mg LY3023703	0.5 mg LY3023703	2.5 mg LY3023703	10 mg LY3023703	30 mg LY3023703	60 mg LY3023703	Celecoxib
Arm/Group Description	Matched placebo capsules administered orally in Periods 1 or 2.	0.1-milligram (mg) LY3023703 capsule administered orally, once in Period 1.	0.5-mg LY3023703 capsule administered orally, once in Period 1.	2.5-mg LY3023703 capsule administered orally, once in Period 1.	10-mg LY3023703 capsule administered orally, once in Period 2.	30-mg LY3023703 capsule administered orally, once in Period 2.	60-mg LY3023703 capsule administered orally, once in Period 2.	400-mg celecoxib dose (two 200-mg celecoxib capsules) administered orally, once in Period 3.
Measure Participants	12	8	8	8	7	8	7	27
Percent Change at 0 to 2 h	-6.4	-34.6	15.5	22.4	-1.2	33.1	27.7	-32.0
Percent Change at 2 to 4 h	-10.9	-19.6	18.6	9.8	29.3	51.5	74.5	-66.0
Percent Change at 4 to 6 h	-0.9	-19.1	-3.5	3.7	-0.9	19.5	63.3	-60.0
Percent Change at 6 to 12 h	-6.1	-29.8	13.6	0.6	98.4	44.1	49.9	-45.2

7. Secondary Outcome

Title	Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM)
Description	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

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug or placebo and had evaluable TXAM data at specific time points.

Arm/Group Title	Placebo	0.1 mg LY3023703	0.5 mg LY3023703	2.5 mg LY3023703	10 mg LY3023703	30 mg LY3023703	60 mg LY3023703	Celecoxib
Arm/Group Description	Matched placebo capsules administered orally in Periods 1 or 2.	0.1-milligram (mg) LY3023703 capsule administered orally, once in Period 1.	0.5-mg LY3023703 capsule administered orally, once in Period 1.	2.5-mg LY3023703 capsule administered orally, once in Period 1.	10-mg LY3023703 capsule administered orally, once in Period 2.	30-mg LY3023703 capsule administered orally, once in Period 2.	60-mg LY3023703 capsule administered orally, once in Period 2.	400-mg celecoxib dose (two 200-mg celecoxib capsules) administered orally, once in Period 3.
Measure Participants	12	8	8	8	7	8	7	27
Percent Change at 0 to 2 h	-9.1	-19.9	6.5	-17.9	8.7	2.7	-10.2	-5.0
Percent Change at 2 to 4 h	-12.5	-11.5	11.1	-7.9	21.4	26.3	13.0	-17.7
Percent Change at 4 to 6 h	-15.0	-19.8	2.6	-18.8	16.4	-13.1	18.5	-25.7
Percent Change at 6 to 12 h	-8.7	-13.8	7.7	-19.2	18.0	9.8	19.1	-16.2

Adverse Events

Arm/Group Title	Placebo		LY3023703 0.1 mg		LY3023703 0.5 mg		LY3023703 2.5 mg		LY3023703 10 mg		LY3023703 30 mg		LY3023703 60 mg		Celecoxib
Arm/Group Description	Matched placebo capsules administered orally in Periods 1 or 2.		0.1-milligram (mg) LY3023703 capsule administered orally, once in Period 1.		0.5-mg LY3023703 capsule administered orally, once in Period 1.		2.5-mg LY3023703 capsule administered orally, once in Period 1.		10-mg LY3023703 capsule administered orally, once in Period 2.		30-mg LY3023703 capsule administered orally, once in Period 2.		60-mg LY3023703 capsule administered orally, once in Period 2.		400-mg celecoxib capsule, administered orally, once in Period 3.
All Cause Mortality
	Placebo		LY3023703 0.1 mg		LY3023703 0.5 mg		LY3023703 2.5 mg		LY3023703 10 mg		LY3023703 30 mg		LY3023703 60 mg		Celecoxib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		LY3023703 0.1 mg		LY3023703 0.5 mg		LY3023703 2.5 mg		LY3023703 10 mg		LY3023703 30 mg		LY3023703 60 mg		Celecoxib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/8 (0%)		0/8 (0%)		0/8 (0%)		0/7 (0%)		0/8 (0%)		0/8 (0%)		0/28 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		LY3023703 0.1 mg		LY3023703 0.5 mg		LY3023703 2.5 mg		LY3023703 10 mg		LY3023703 30 mg		LY3023703 60 mg		Celecoxib
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/12 (25%)		1/8 (12.5%)		0/8 (0%)		2/8 (25%)		0/7 (0%)		4/8 (50%)		2/8 (25%)		2/28 (7.1%)
Eye disorders
Lacrimation increased	0/12 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/28 (0%)	0
Infections and infestations
Cytomegalovirus infection	0/12 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/28 (0%)	0
Upper respiratory tract infection	1/12 (8.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/28 (0%)	0
Viral upper respiratory tract infection	0/12 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/28 (0%)	0
Injury, poisoning and procedural complications
Arthropod bite	0/12 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/28 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/12 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/8 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/28 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/12 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	0/8 (0%)	0	0/28 (0%)	0
Myalgia	0/12 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/7 (0%)	0	1/8 (12.5%)	1	1/8 (12.5%)	2	0/28 (0%)	0
Pain in extremity	0/12 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	2	0/28 (0%)	0
Temporomandibular joint syndrome	0/12 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/28 (3.6%)	1
Nervous system disorders
Headache	2/12 (16.7%)	2	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	2/8 (25%)	2	1/28 (3.6%)	1
Respiratory, thoracic and mediastinal disorders
Nasal congestion	0/12 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	1/8 (12.5%)	1	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/28 (0%)	0
Skin and subcutaneous tissue disorders
Urticaria	1/12 (8.3%)	1	0/8 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/7 (0%)	0	0/8 (0%)	0	0/8 (0%)	0	0/28 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.