Trial Outcomes & Findings for A Single Dose Study of LY3023703 in Healthy Participants (NCT NCT01632579)
NCT ID: NCT01632579
Last Updated: 2018-08-06
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
Baseline up to Day 7 post-dose
Results posted on
2018-08-06
Participant Flow
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.
Participant milestones
| Measure |
Cohort 1 Sequence 1
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.
|
Cohort 1 Sequence 2
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.
|
Cohort 1 Sequence 3
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.
|
Cohort 2 Sequence 1
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.
|
Cohort 2 Sequence 2
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.
|
Cohort 2 Sequence 3
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.
|
Cohort 3 Sequence 1
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.
|
Cohort 3 Sequence 2
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.
|
Cohort 3 Sequence 3
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 1 (First Intervention)
STARTED
|
2
|
6
|
2
|
2
|
6
|
2
|
2
|
6
|
2
|
|
Period 1 (First Intervention)
Received at Least 1 Dose
|
2
|
6
|
2
|
2
|
6
|
2
|
2
|
6
|
2
|
|
Period 1 (First Intervention)
COMPLETED
|
2
|
6
|
2
|
2
|
6
|
2
|
2
|
6
|
2
|
|
Period 1 (First Intervention)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period
STARTED
|
0
|
6
|
2
|
2
|
6
|
2
|
2
|
6
|
2
|
|
Washout Period
COMPLETED
|
0
|
6
|
2
|
2
|
6
|
2
|
2
|
6
|
2
|
|
Washout Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 2 (Second Intervention)
STARTED
|
1
|
6
|
2
|
2
|
6
|
2
|
2
|
6
|
2
|
|
Period 2 (Second Intervention)
Received at Least 1 Dose
|
1
|
6
|
2
|
2
|
6
|
2
|
2
|
6
|
2
|
|
Period 2 (Second Intervention)
COMPLETED
|
0
|
6
|
2
|
2
|
6
|
2
|
2
|
6
|
2
|
|
Period 2 (Second Intervention)
NOT COMPLETED
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 3 (Third Intervention)
STARTED
|
0
|
6
|
2
|
2
|
6
|
2
|
2
|
6
|
2
|
|
Period 3 (Third Intervention)
Received at Least 1 Dose
|
0
|
6
|
2
|
2
|
6
|
2
|
2
|
6
|
2
|
|
Period 3 (Third Intervention)
COMPLETED
|
0
|
6
|
2
|
2
|
6
|
2
|
2
|
6
|
2
|
|
Period 3 (Third Intervention)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Cohort 1 Sequence 1
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.
|
Cohort 1 Sequence 2
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.
|
Cohort 1 Sequence 3
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.
|
Cohort 2 Sequence 1
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.
|
Cohort 2 Sequence 2
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.
|
Cohort 2 Sequence 3
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.
|
Cohort 3 Sequence 1
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.
|
Cohort 3 Sequence 2
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.
|
Cohort 3 Sequence 3
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.
|
|---|---|---|---|---|---|---|---|---|---|
|
Washout Period
Adverse Event
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 2 (Second Intervention)
Adverse Event
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
Baseline Characteristics
A Single Dose Study of LY3023703 in Healthy Participants
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=30 Participants
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.
|
|---|---|
|
Age, Continuous
|
47.0 years
STANDARD_DEVIATION 10.9 • n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
29 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
26 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline up to Day 7 post-dosePopulation: Safety population: participants who received at least 1 dose of study drug or placebo, whether or not he/she completed all the protocol requirements.
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Matched placebo capsules administered orally in Periods 1 or 2.
|
0.1 mg LY3023703
n=8 Participants
0.1-milligram (mg) LY3023703 capsule administered orally, once in Period 1.
|
0.5 mg LY3023703
n=8 Participants
0.5-mg LY3023703 capsule administered orally, once in Period 1.
|
2.5 mg LY3023703
n=8 Participants
2.5-mg LY3023703 capsule administered orally, once in Period 1.
|
10 mg LY3023703
n=7 Participants
10-mg LY3023703 capsule administered orally, once in Period 2.
|
30 mg LY3023703
n=8 Participants
30-mg LY3023703 capsule administered orally, once in Period 2.
|
60 mg LY3023703
n=8 Participants
60-mg LY3023703 capsule administered orally, once in Period 2.
|
Celecoxib
n=28 Participants
400-mg celecoxib dose (two 200-mg celecoxib capsules) administered orally, once in Period 3.
|
|---|---|---|---|---|---|---|---|---|
|
Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE
Any Serious AE
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AE
Drug-Related AE
|
3 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 8 and 12 hours, post-dosePopulation: Pharmacokinetic (PK) population: participants who received at least 1 dose of study drug and had evaluable Cmax data.
Outcome measures
| Measure |
Placebo
n=8 Participants
Matched placebo capsules administered orally in Periods 1 or 2.
|
0.1 mg LY3023703
n=8 Participants
0.1-milligram (mg) LY3023703 capsule administered orally, once in Period 1.
|
0.5 mg LY3023703
n=8 Participants
0.5-mg LY3023703 capsule administered orally, once in Period 1.
|
2.5 mg LY3023703
n=7 Participants
2.5-mg LY3023703 capsule administered orally, once in Period 1.
|
10 mg LY3023703
n=8 Participants
10-mg LY3023703 capsule administered orally, once in Period 2.
|
30 mg LY3023703
n=8 Participants
30-mg LY3023703 capsule administered orally, once in Period 2.
|
60 mg LY3023703
60-mg LY3023703 capsule administered orally, once in Period 2.
|
Celecoxib
400-mg celecoxib dose (two 200-mg celecoxib capsules) administered orally, once in Period 3.
|
|---|---|---|---|---|---|---|---|---|
|
Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703
|
1.15 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 25.4
|
5.66 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 27.7
|
23.5 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 23.7
|
140 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 22.0
|
547 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 36.0
|
756 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 26.8
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1: pre-dose, 0.25, 0.5, 1, 2, 4, 8 and 12 hours, post-dosePopulation: Pharmacokinetic (PK) population: All participants who received at least 1 dose of study drug and had evaluable AUC data.
Area under the concentration time curve from the time of dosing to the time of the last observation.
Outcome measures
| Measure |
Placebo
n=8 Participants
Matched placebo capsules administered orally in Periods 1 or 2.
|
0.1 mg LY3023703
n=8 Participants
0.1-milligram (mg) LY3023703 capsule administered orally, once in Period 1.
|
0.5 mg LY3023703
n=8 Participants
0.5-mg LY3023703 capsule administered orally, once in Period 1.
|
2.5 mg LY3023703
n=7 Participants
2.5-mg LY3023703 capsule administered orally, once in Period 1.
|
10 mg LY3023703
n=8 Participants
10-mg LY3023703 capsule administered orally, once in Period 2.
|
30 mg LY3023703
n=8 Participants
30-mg LY3023703 capsule administered orally, once in Period 2.
|
60 mg LY3023703
60-mg LY3023703 capsule administered orally, once in Period 2.
|
Celecoxib
400-mg celecoxib dose (two 200-mg celecoxib capsules) administered orally, once in Period 3.
|
|---|---|---|---|---|---|---|---|---|
|
Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3023703
|
3.19 hour*nanograms per milliliter (hr*ng/mL)
Geometric Coefficient of Variation 52.0
|
54.7 hour*nanograms per milliliter (hr*ng/mL)
Geometric Coefficient of Variation 72.4
|
245 hour*nanograms per milliliter (hr*ng/mL)
Geometric Coefficient of Variation 58.5
|
1680 hour*nanograms per milliliter (hr*ng/mL)
Geometric Coefficient of Variation 36.8
|
9940 hour*nanograms per milliliter (hr*ng/mL)
Geometric Coefficient of Variation 45.6
|
13800 hour*nanograms per milliliter (hr*ng/mL)
Geometric Coefficient of Variation 30.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, 0.5 hours (h), 1 h, 2 h, 8 h, 24 h, and 144 h post-dosePopulation: All participants who received at least 1 dose of study drug or placebo and had evaluable PGE data at the specific time points.
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).
Outcome measures
| Measure |
Placebo
n=11 Participants
Matched placebo capsules administered orally in Periods 1 or 2.
|
0.1 mg LY3023703
n=1 Participants
0.1-milligram (mg) LY3023703 capsule administered orally, once in Period 1.
|
0.5 mg LY3023703
n=8 Participants
0.5-mg LY3023703 capsule administered orally, once in Period 1.
|
2.5 mg LY3023703
n=8 Participants
2.5-mg LY3023703 capsule administered orally, once in Period 1.
|
10 mg LY3023703
n=7 Participants
10-mg LY3023703 capsule administered orally, once in Period 2.
|
30 mg LY3023703
n=8 Participants
30-mg LY3023703 capsule administered orally, once in Period 2.
|
60 mg LY3023703
n=8 Participants
60-mg LY3023703 capsule administered orally, once in Period 2.
|
Celecoxib
n=28 Participants
400-mg celecoxib dose (two 200-mg celecoxib capsules) administered orally, once in Period 3.
|
|---|---|---|---|---|---|---|---|---|
|
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
Interval -68.0 to -19.4
|
-31.1 percent change in PGE
Interval -31.1 to -31.1
|
20.5 percent change in PGE
Interval -32.0 to 66.6
|
28.9 percent change in PGE
Interval -25.3 to 103.9
|
111.6 percent change in PGE
Interval 66.9 to 117.9
|
-61.3 percent change in PGE
Interval -115.7 to 68.6
|
4.3 percent change in PGE
Interval -21.2 to 36.0
|
11.6 percent change in PGE
Interval -28.8 to 190.4
|
|
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
Interval -36.7 to 71.2
|
102.6 percent change in PGE
Interval 102.6 to 102.6
|
-11.6 percent change in PGE
Interval -34.0 to 3.3
|
29.3 percent change in PGE
Interval -9.0 to 91.4
|
-12.1 percent change in PGE
Interval -37.9 to 22.2
|
-43.5 percent change in PGE
Interval -65.6 to -14.3
|
-27.1 percent change in PGE
Interval -46.8 to -4.5
|
-7.1 percent change in PGE
Interval -23.6 to 44.6
|
|
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
Interval -43.9 to 71.5
|
106.4 percent change in PGE
Interval 106.4 to 106.4
|
-6.2 percent change in PGE
Interval -46.4 to 27.3
|
-18.9 percent change in PGE
Interval -46.8 to 21.8
|
-67.6 percent change in PGE
Interval -76.9 to -23.8
|
-84.1 percent change in PGE
Interval -99.8 to -77.7
|
-82.4 percent change in PGE
Interval -95.1 to -62.1
|
-14.0 percent change in PGE
Interval -47.1 to 10.5
|
|
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
Interval -27.1 to 103.2
|
87.9 percent change in PGE
Interval 87.9 to 87.9
|
52.1 percent change in PGE
Interval 4.9 to 61.5
|
-59.6 percent change in PGE
Interval -64.6 to -21.9
|
-82.7 percent change in PGE
Interval -92.3 to -74.3
|
-102.0 percent change in PGE
Interval -130.1 to -97.0
|
-89.1 percent change in PGE
Interval -93.9 to -76.8
|
-42.5 percent change in PGE
Interval -60.0 to -25.2
|
|
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
Interval -28.4 to 75.8
|
44.2 percent change in PGE
Interval 44.2 to 44.2
|
90.5 percent change in PGE
Interval 76.6 to 113.7
|
3.3 percent change in PGE
Interval -16.1 to 40.1
|
-56.0 percent change in PGE
Interval -81.9 to -52.0
|
-96.5 percent change in PGE
Interval -111.8 to -94.4
|
-96.1 percent change in PGE
Interval -100.6 to -87.4
|
-26.7 percent change in PGE
Interval -42.7 to 6.5
|
|
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
Interval -47.1 to 8.8
|
—
|
44.1 percent change in PGE
Interval 27.5 to 65.0
|
-7.6 percent change in PGE
Interval -14.7 to 84.1
|
16.1 percent change in PGE
Interval -29.9 to 94.4
|
-84.2 percent change in PGE
Interval -87.1 to -78.1
|
-80.7 percent change in PGE
Interval -85.6 to -64.2
|
-21.8 percent change in PGE
Interval -49.9 to 21.0
|
SECONDARY outcome
Timeframe: Baseline, 0 to 2 hours (h), 2 to 4 h, 4 to 6 h, 6 to 12 h, and 12 to 24 hours post-dosePopulation: All participants who received at least 1 dose of study drug or placebo and had evaluable PGEM data at specific time points.
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Matched placebo capsules administered orally in Periods 1 or 2.
|
0.1 mg LY3023703
n=8 Participants
0.1-milligram (mg) LY3023703 capsule administered orally, once in Period 1.
|
0.5 mg LY3023703
n=8 Participants
0.5-mg LY3023703 capsule administered orally, once in Period 1.
|
2.5 mg LY3023703
n=8 Participants
2.5-mg LY3023703 capsule administered orally, once in Period 1.
|
10 mg LY3023703
n=7 Participants
10-mg LY3023703 capsule administered orally, once in Period 2.
|
30 mg LY3023703
n=8 Participants
30-mg LY3023703 capsule administered orally, once in Period 2.
|
60 mg LY3023703
n=7 Participants
60-mg LY3023703 capsule administered orally, once in Period 2.
|
Celecoxib
n=27 Participants
400-mg celecoxib dose (two 200-mg celecoxib capsules) administered orally, once in Period 3.
|
|---|---|---|---|---|---|---|---|---|
|
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
Interval -26.3 to 30.2
|
7.4 percent change in PGEM
Interval -35.3 to 14.7
|
-4.0 percent change in PGEM
Interval -19.7 to 19.8
|
1.5 percent change in PGEM
Interval -15.8 to 17.6
|
-5.3 percent change in PGEM
Interval -21.0 to 47.5
|
17.7 percent change in PGEM
Interval -24.8 to 35.9
|
-6.6 percent change in PGEM
Interval -25.8 to 52.0
|
-7.5 percent change in PGEM
Interval -28.3 to 11.3
|
|
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
Interval -30.1 to 52.0
|
0.7 percent change in PGEM
Interval -19.4 to 20.4
|
7.9 percent change in PGEM
Interval -15.8 to 30.3
|
-0.8 percent change in PGEM
Interval -25.8 to 5.3
|
-21.0 percent change in PGEM
Interval -44.8 to 7.8
|
-46.6 percent change in PGEM
Interval -52.3 to -24.0
|
-25.1 percent change in PGEM
Interval -47.7 to 25.2
|
-41.5 percent change in PGEM
Interval -51.3 to -21.4
|
|
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
Interval -33.7 to 20.6
|
-0.0 percent change in PGEM
Interval -37.8 to 2.9
|
-25.0 percent change in PGEM
Interval -42.4 to -8.9
|
-19.0 percent change in PGEM
Interval -39.7 to -6.7
|
-29.1 percent change in PGEM
Interval -51.6 to -9.0
|
-53.0 percent change in PGEM
Interval -62.5 to -35.7
|
-42.4 percent change in PGEM
Interval -57.3 to 26.9
|
-55.0 percent change in PGEM
Interval -70.3 to -42.6
|
|
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
Interval -45.5 to 11.9
|
-18.5 percent change in PGEM
Interval -36.7 to 7.3
|
2.3 percent change in PGEM
Interval -31.1 to 10.8
|
-20.4 percent change in PGEM
Interval -27.4 to -7.2
|
-39.5 percent change in PGEM
Interval -57.9 to -23.4
|
-37.5 percent change in PGEM
Interval -62.3 to -19.2
|
-48.0 percent change in PGEM
Interval -58.0 to -9.5
|
-49.7 percent change in PGEM
Interval -68.9 to -27.8
|
|
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
Interval -39.3 to 8.6
|
-38.8 percent change in PGEM
Interval -42.1 to -22.9
|
-18.0 percent change in PGEM
Interval -35.8 to 9.2
|
-19.1 percent change in PGEM
Interval -39.9 to -3.5
|
-28.8 percent change in PGEM
Interval -42.6 to 43.3
|
-31.2 percent change in PGEM
Interval -47.7 to -8.6
|
-53.0 percent change in PGEM
Interval -74.9 to -19.9
|
-46.2 percent change in PGEM
Interval -59.2 to -11.4
|
SECONDARY outcome
Timeframe: Baseline, 0 to 2 hours (h), 2 to 4 h, 4 to 6 h, and 6 to 12 h post-dosePopulation: All participants who received at least 1 dose of study drug or placebo and had evaluable PGIM data at specific time points.
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Matched placebo capsules administered orally in Periods 1 or 2.
|
0.1 mg LY3023703
n=8 Participants
0.1-milligram (mg) LY3023703 capsule administered orally, once in Period 1.
|
0.5 mg LY3023703
n=8 Participants
0.5-mg LY3023703 capsule administered orally, once in Period 1.
|
2.5 mg LY3023703
n=8 Participants
2.5-mg LY3023703 capsule administered orally, once in Period 1.
|
10 mg LY3023703
n=7 Participants
10-mg LY3023703 capsule administered orally, once in Period 2.
|
30 mg LY3023703
n=8 Participants
30-mg LY3023703 capsule administered orally, once in Period 2.
|
60 mg LY3023703
n=7 Participants
60-mg LY3023703 capsule administered orally, once in Period 2.
|
Celecoxib
n=27 Participants
400-mg celecoxib dose (two 200-mg celecoxib capsules) administered orally, once in Period 3.
|
|---|---|---|---|---|---|---|---|---|
|
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
Interval -21.6 to 19.6
|
-34.6 percent change in PGIM
Interval -50.5 to -13.2
|
15.5 percent change in PGIM
Interval -0.9 to 46.2
|
22.4 percent change in PGIM
Interval 3.5 to 41.9
|
-1.2 percent change in PGIM
Interval -27.3 to 23.7
|
33.1 percent change in PGIM
Interval -11.9 to 91.1
|
27.7 percent change in PGIM
Interval -15.6 to 102.0
|
-32.0 percent change in PGIM
Interval -39.2 to -16.2
|
|
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
Interval -34.5 to -2.2
|
-19.6 percent change in PGIM
Interval -34.3 to -13.7
|
18.6 percent change in PGIM
Interval -18.5 to 49.2
|
9.8 percent change in PGIM
Interval -3.3 to 64.5
|
29.3 percent change in PGIM
Interval 10.0 to 58.8
|
51.5 percent change in PGIM
Interval 16.3 to 65.6
|
74.5 percent change in PGIM
Interval -29.6 to 128.2
|
-66.0 percent change in PGIM
Interval -75.9 to -46.5
|
|
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
Interval -29.6 to 29.7
|
-19.1 percent change in PGIM
Interval -58.5 to -5.8
|
-3.5 percent change in PGIM
Interval -13.7 to 11.9
|
3.7 percent change in PGIM
Interval -17.3 to 23.2
|
-0.9 percent change in PGIM
Interval -27.4 to 36.4
|
19.5 percent change in PGIM
Interval -2.6 to 67.4
|
63.3 percent change in PGIM
Interval -18.3 to 138.3
|
-60.0 percent change in PGIM
Interval -68.2 to -53.1
|
|
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
Interval -11.0 to 15.9
|
-29.8 percent change in PGIM
Interval -35.3 to 39.4
|
13.6 percent change in PGIM
Interval -0.1 to 19.6
|
0.6 percent change in PGIM
Interval -7.6 to 37.6
|
98.4 percent change in PGIM
Interval 4.9 to 112.3
|
44.1 percent change in PGIM
Interval 14.0 to 98.3
|
49.9 percent change in PGIM
Interval -10.9 to 138.7
|
-45.2 percent change in PGIM
Interval -57.7 to -23.6
|
SECONDARY outcome
Timeframe: Baseline, 0 to 2 hours (h), 2 to 4 h, 4 to 6 h, and 6 to 12 h post-dosePopulation: All participants who received at least 1 dose of study drug or placebo and had evaluable TXAM data at specific time points.
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.
Outcome measures
| Measure |
Placebo
n=12 Participants
Matched placebo capsules administered orally in Periods 1 or 2.
|
0.1 mg LY3023703
n=8 Participants
0.1-milligram (mg) LY3023703 capsule administered orally, once in Period 1.
|
0.5 mg LY3023703
n=8 Participants
0.5-mg LY3023703 capsule administered orally, once in Period 1.
|
2.5 mg LY3023703
n=8 Participants
2.5-mg LY3023703 capsule administered orally, once in Period 1.
|
10 mg LY3023703
n=7 Participants
10-mg LY3023703 capsule administered orally, once in Period 2.
|
30 mg LY3023703
n=8 Participants
30-mg LY3023703 capsule administered orally, once in Period 2.
|
60 mg LY3023703
n=7 Participants
60-mg LY3023703 capsule administered orally, once in Period 2.
|
Celecoxib
n=27 Participants
400-mg celecoxib dose (two 200-mg celecoxib capsules) administered orally, once in Period 3.
|
|---|---|---|---|---|---|---|---|---|
|
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
Interval -24.2 to 3.4
|
-19.9 percent change in TXAM
Interval -23.6 to -8.4
|
6.5 percent change in TXAM
Interval -14.1 to 32.4
|
-17.9 percent change in TXAM
Interval -29.7 to -5.8
|
8.7 percent change in TXAM
Interval -17.2 to 17.0
|
2.7 percent change in TXAM
Interval -13.4 to 30.4
|
-10.2 percent change in TXAM
Interval -19.8 to -0.1
|
-5.0 percent change in TXAM
Interval -22.5 to 9.8
|
|
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
Interval -23.4 to 3.4
|
-11.5 percent change in TXAM
Interval -25.5 to -3.7
|
11.1 percent change in TXAM
Interval -4.8 to 23.0
|
-7.9 percent change in TXAM
Interval -23.8 to 2.1
|
21.4 percent change in TXAM
Interval 13.6 to 31.3
|
26.3 percent change in TXAM
Interval 4.1 to 43.1
|
13.0 percent change in TXAM
Interval -2.3 to 37.3
|
-17.7 percent change in TXAM
Interval -30.8 to -5.9
|
|
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
Interval -21.4 to 2.1
|
-19.8 percent change in TXAM
Interval -24.3 to -5.7
|
2.6 percent change in TXAM
Interval -4.7 to 12.3
|
-18.8 percent change in TXAM
Interval -20.9 to -13.6
|
16.4 percent change in TXAM
Interval -1.0 to 32.5
|
-13.1 percent change in TXAM
Interval -25.2 to 7.4
|
18.5 percent change in TXAM
Interval -3.7 to 22.0
|
-25.7 percent change in TXAM
Interval -37.8 to -18.0
|
|
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
Interval -21.5 to 5.5
|
-13.8 percent change in TXAM
Interval -20.1 to -8.6
|
7.7 percent change in TXAM
Interval -2.2 to 11.7
|
-19.2 percent change in TXAM
Interval -23.1 to -12.3
|
18.0 percent change in TXAM
Interval 8.7 to 28.8
|
9.8 percent change in TXAM
Interval -12.1 to 37.7
|
19.1 percent change in TXAM
Interval 14.6 to 31.8
|
-16.2 percent change in TXAM
Interval -26.0 to -4.8
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
LY3023703 0.1 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
LY3023703 0.5 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
LY3023703 2.5 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
LY3023703 10 mg
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
LY3023703 30 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
LY3023703 60 mg
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Celecoxib
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Placebo
n=12 participants at risk
Matched placebo capsules administered orally in Periods 1 or 2.
|
LY3023703 0.1 mg
n=8 participants at risk
0.1-milligram (mg) LY3023703 capsule administered orally, once in Period 1.
|
LY3023703 0.5 mg
n=8 participants at risk
0.5-mg LY3023703 capsule administered orally, once in Period 1.
|
LY3023703 2.5 mg
n=8 participants at risk
2.5-mg LY3023703 capsule administered orally, once in Period 1.
|
LY3023703 10 mg
n=7 participants at risk
10-mg LY3023703 capsule administered orally, once in Period 2.
|
LY3023703 30 mg
n=8 participants at risk
30-mg LY3023703 capsule administered orally, once in Period 2.
|
LY3023703 60 mg
n=8 participants at risk
60-mg LY3023703 capsule administered orally, once in Period 2.
|
Celecoxib
n=28 participants at risk
400-mg celecoxib capsule, administered orally, once in Period 3.
|
|---|---|---|---|---|---|---|---|---|
|
Eye disorders
Lacrimation increased
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/7
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/28
|
|
Infections and infestations
Cytomegalovirus infection
|
0.00%
0/12
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/7
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/28
|
|
Infections and infestations
Upper respiratory tract infection
|
8.3%
1/12 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/7
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/28
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/7
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/28
|
|
Injury, poisoning and procedural complications
Arthropod bite
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/7
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/28
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/12
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/7
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/28
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/7
|
12.5%
1/8 • Number of events 1
|
0.00%
0/8
|
0.00%
0/28
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/7
|
12.5%
1/8 • Number of events 1
|
12.5%
1/8 • Number of events 2
|
0.00%
0/28
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/7
|
0.00%
0/8
|
12.5%
1/8 • Number of events 2
|
0.00%
0/28
|
|
Musculoskeletal and connective tissue disorders
Temporomandibular joint syndrome
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/7
|
0.00%
0/8
|
0.00%
0/8
|
3.6%
1/28 • Number of events 1
|
|
Nervous system disorders
Headache
|
16.7%
2/12 • Number of events 2
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/7
|
0.00%
0/8
|
25.0%
2/8 • Number of events 2
|
3.6%
1/28 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/12
|
0.00%
0/8
|
0.00%
0/8
|
12.5%
1/8 • Number of events 1
|
0.00%
0/7
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/28
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
8.3%
1/12 • Number of events 1
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/7
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/28
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Phone: 800-545-5979
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60