Healthy Volunteers
Conditions
Brief summary
This is a phase I study of LY3031207 in healthy subjects. The purposes of this study are to look at safety, how well the study drug is tolerated, and 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. Subjects will participate 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
* Male subjects agree to use a reliable method of birth control during the study and for 3 months following the last dose of the investigational product * Women not of child-bearing potential due to surgical sterilization (at least 6 weeks after surgical bilateral oophorectomy with or without hysterectomy or at least 6 weeks after tubal ligation) confirmed by medical history or menopause * Menopausal women include women with either spontaneous amenorrhea for at least 12 months, not induced by a medical condition such as anorexia nervosa and not taking medications during the amenorrhea that induced the amenorrhea (for example \[e.g.\], oral contraceptives, hormones, gonadotropin-releasing hormone, antiestrogens, selective estrogen receptor modulators, or chemotherapy) or spontaneous amenorrhea for 6 to 12 months and a follicle-stimulating hormone level greater than 40 milli-International Unit (mIU/mL) * Overtly healthy based on the history and physical examinations as determined by the investigator * Between body mass index (BMI) of 18.5 and 32.0 kilogram per meter squared (kg/m\^2), inclusive * Normotensive defined as supine systolic blood pressure (BP) \<140 of millimeter mercury (mmHg), and diastolic BP \<90 mmHg, without the use of any antihypertensives, or results that are judged to be not clinically significant by the Investigator. Blood pressure may be retested up to 2 additional times, under well rested conditions * Clinical laboratory test results within normal reference range for the population or investigator site, or results with acceptable deviations that are judged to be not clinically significant by the investigator * Ex vivo whole blood prostaglandin E(PGE) synthesis after lipopolysaccharide (LPS) stimulation of no less than 5 nanograms/milliliter (ng/mL). * Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures * Have given written informed consent approved by Lilly and the ethical review board (ERB) governing the site
Exclusion criteria
* Are currently enrolled in, have completed or discontinued within the last 30 days from, a clinical trial involving an investigational product or unapproved use of a drug with a short half-life, or within 5 half-life of an investigational product with a half-life longer than 5 days, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study * Have known allergies to LY3031207 or any components of the formulation, celecoxib or sulfonamides. Subjects with known aspirin allergy or allergic reaction to non-steroidal anti-inflammatory drugs (NSAIDs) should also be excluded * Are persons who have previously completed or withdrawn from this study or any other study investigating LY3031207 and who have previously received the investigational product * Have an abnormality in the 12-lead Electrocardiogram (ECG), including QTc interval with Bazett's correction \>450 millisecond (msec) for men and \>470 msec for women or an abnormality that, in the opinion of the investigator, increases the risks associated with participating in the study. Electrocardiogram may be repeated after 5 minutes resting quietly, if the subject's heart rate is \>75 beats per minute * History of, within the last 2 years, or presence of active cardiovascular disease, including acute myocardial infarction, unstable angina, congestive heart failure, stroke, or transient ischemic attack * Presence of clinically significant active bleeding or history of bleeding diathesis at the time of screening * Presence of active peptic ulcer disease, Gastrointestinal (GI) bleeding, chronic gastritis, inflammatory bowel disease, chronic diarrhea, or positive H. pylori serology * Evidence of hepatitis C and/or positive hepatitis C antibody * Evidence of hepatitis B and/or positive hepatitis B surface antigen * Evidence of other chronic liver disease, including chronic alcoholic disease; non-alcoholic steatohepatitis; recent (within 3 months of screening) history of acute viral hepatitis; or subjects with known Gilbert Syndrome * History of active neuropsychiatric disease * Evidence of human immunodeficiency virus (HIV) infection and/or positive HIV antibodies * Have a significant history of or current other cardiovascular, respiratory (especially asthma and chronic obstructive pulmonary disease), hepatic, renal, GI, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data. History of prior surgeries (at least 3 months prior to dosing), such as splenectomy, cholecystectomy, and appendectomy are not exclusionary * Regularly use of known drugs of abuse and/or show positive findings on urinary drug screening * Are women with a positive pregnancy test or women who are lactating * Intended use of over-the-counter medications or prescription medication within 14 days prior to dosing, this includes but is not limited to antihypertensives, diuretics, antiplatelet or anticoagulant drugs, and antidepressants * Any use of NSAIDs, celecoxib, aspirin or acetaminophen (at doses \>1 gram \[gm\] per day) within 14 days of screening * Any use of herbal or dietary supplements, or grapefruit and/or grapefruit juice, Seville oranges, starfruit, or pomegranate within 14 days prior to dosing of study drug * Have donated blood of more than 500 milliliter (mL) within the last month * Have an average weekly alcohol intake that exceeds 21 units per week (males) and 14 units per week (females) or are unwilling to stop alcohol consumption for the duration of the study (1 unit = 12 ounce \[oz\] or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits). * Subjects who smoke more than 10 cigarettes per day or are unwilling to follow the Clinical Research Unit (CRU) smoking rules * Subjects with any major surgery within 30 days prior to screening or subjects with planned surgeries to occur during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Baseline, up to 4 months | 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 drug relatedness, is located in the Reported Adverse Event module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207 | Predose, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 96, 144 hours post dose | — |
| Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | Predose, 0.5, 1, 2, 8, 24 and 144 hours post dose. | The effect of LY3031207 on PGE synthesis in whole blood after ex vivo LPS stimulation. |
| Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of LY3031207 | Predose, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 96, 144 hours post dose | AUC from time 0 to last timepoint (AUC0-tlast) with measurable concentration of LY3031207. |
| Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | 0 to 2, 2 to 4, 4 to 6, and 6 to 12 hours post dose | The participant's urine was collected during protocol-defined intervals and the PGE metabolite PGIM was assessed. PGIM results for each interval were then compared to the baseline value. |
| Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | 0 to 2, 2 to 4, 4 to 6, and 6 to 12 hours post dose | The participant's urine was collected during protocol-defined intervals and the PGE metabolite TXAM was assessed. TXAM results for each interval were then compared to the baseline value. |
| Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 0 to 2, 2 to 4, 4 to 6, 6 to 12 and 12 to 24 hours post dose | The participant's urine was collected during protocol-defined intervals and the PGE metabolite PGEM was assessed. PGEM results for each interval were then compared to the baseline value. |
Countries
United States
Participant flow
Pre-assignment details
Three period crossover study with three dosing cohorts. The interval between the initiation of each dosing cohort was approximately 1 week, and the washout time between each dosing period was approximately 3 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Cohort I Sequence 1 Participants received 5 mg LY3031207, Placebo and 400 mg Celecoxib as per the below dosing schedule.
Period 1: 5 mg LY3031207 , Period 2: Placebo, and Period 3: 400 mg Celecoxib | 2 |
| Cohort I Sequence 2 Participants received 5 mg LY3031207, 225 mg LY3031207 and 400 mg Celecoxib as per the below dosing schedule.
Period 1: 5 mg LY3031207, Period 2: 225 mg LY3031207 and Period 3: 400 mg Celecoxib | 6 |
| Cohort I Sequence 3 Participants received Placebo, 225 mg LY3031207 and 400 mg Celecoxib as per the below dosing schedule.
Period 1: Placebo, Period 2: 225 mg LY3031207 and Period 3: 400 mg Celecoxib | 2 |
| Cohort II Sequence 1 Participants received 25 mg LY3031207 and Placebo as per the below dosing schedule.
Period 1: 25 mg LY3031207, Period 2: Placebo and Period 3: Placebo | 2 |
| Cohort II Sequence 2 Participants received 25 mg LY3031207, 450 mg LY3031207 (Fed condition) and 450 mg LY3031207 (Fasted) as per the below dosing schedule.
Period 1: 25 mg LY3031207, Period 2: 450 mg LY3031207 (Fed) and Period 3: 450 mg LY3031207 (Fasted) | 5 |
| Cohort II Sequence 3 Participants received Placebo, 450 mg LY3031207 (Fed condition) and 450 mg LY3031207 (Fasted) as per the below dosing schedule.
Period 1: Placebo, Period 2: 450 mg LY3031207 (Fed) and Period 3: 450 mg LY3031207 (Fasted) | 2 |
| Cohort III Sequence 1 Participants received LY3031207 75 mg, Placebo and celecoxib as per the below dosing schedule.
Period 1: LY3031207 75 mg, Period 2: Placebo and Period 3: Celecoxib 400 mg | 2 |
| Cohort III Sequence 2 Participants received LY3031207 75 mg, LY3031207 900 mg and celecoxib as per the below dosing schedule.
Period 1: LY3031207 75 mg, Period 2: LY3031207 900 mg and Period 3: Celecoxib 400 mg | 6 |
| Cohort III Sequence 3 Participants received Placebo, LY3031207 900 mg and celecoxib as per the below dosing schedule.
Period 1: Placebo, Period 2: LY3031207 900 mg and Period 3: Celecoxib 400 mg | 2 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 | Physician Decision | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Period 1 | Sponsor Decision | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Period 2 | Sponsor Decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort I Sequence 1 | Cohort III Sequence 3 | Total | Cohort I Sequence 2 | Cohort I Sequence 3 | Cohort II Sequence 1 | Cohort II Sequence 2 | Cohort II Sequence 3 | Cohort III Sequence 1 | Cohort III Sequence 2 |
|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 2 Participants | 29 Participants | 6 Participants | 2 Participants | 2 Participants | 5 Participants | 2 Participants | 2 Participants | 6 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 1 Participants | 1 Participants | 26 Participants | 6 Participants | 2 Participants | 2 Participants | 4 Participants | 2 Participants | 2 Participants | 6 Participants |
| Region of Enrollment United States | 2 Participants | 2 Participants | 29 Participants | 6 Participants | 2 Participants | 2 Participants | 5 Participants | 2 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 9 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 20 Participants | 3 Participants | 1 Participants | 2 Participants | 4 Participants | 1 Participants | 1 Participants | 5 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 | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 8 | 3 / 6 | 1 / 8 | 1 / 7 | 0 / 6 | 2 / 6 | 2 / 8 | 2 / 10 | 1 / 18 |
| serious Total, serious adverse events | 0 / 8 | 0 / 6 | 0 / 8 | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 10 | 0 / 18 |
Outcome results
Primary
Number of Participants With 1 or More Drug Related Adverse Events (AE) 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 drug relatedness, is located in the Reported Adverse Event module.
Time frame: Baseline, up to 4 months
Population: All participants who received at least 1 dose of study drug or placebo.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 5 mg LY3031207 | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Serious AEs | 0 Participants |
| 5 mg LY3031207 | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Other Non-Serious AEs | 3 Participants |
| 25 mg LY3031207 | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Serious AEs | 0 Participants |
| 25 mg LY3031207 | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Other Non-Serious AEs | 3 Participants |
| 75 mg LY3031207 | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Serious AEs | 0 Participants |
| 75 mg LY3031207 | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Other Non-Serious AEs | 1 Participants |
| 225 mg LY3031207 | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Serious AEs | 0 Participants |
| 225 mg LY3031207 | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Other Non-Serious AEs | 1 Participants |
| 450 mg LY3031207 Fed | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Serious AEs | 0 Participants |
| 450 mg LY3031207 Fed | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Other Non-Serious AEs | 0 Participants |
| 450 mg LY3031207 Fasted | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Other Non-Serious AEs | 2 Participants |
| 450 mg LY3031207 Fasted | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Serious AEs | 0 Participants |
| 900 mg LY3031207 | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Other Non-Serious AEs | 2 Participants |
| 900 mg LY3031207 | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Serious AEs | 0 Participants |
| Placebo | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Serious AEs | 0 Participants |
| Placebo | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Other Non-Serious AEs | 2 Participants |
| 400 mg Celecoxib | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Serious AEs | 0 Participants |
| 400 mg Celecoxib | Number of Participants With 1 or More Drug Related Adverse Events (AE) or Any Serious AE | Other Non-Serious AEs | 1 Participants |
Secondary
Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation
The effect of LY3031207 on PGE synthesis in whole blood after ex vivo LPS stimulation.
Time frame: Predose, 0.5, 1, 2, 8, 24 and 144 hours post dose.
Population: All participants who received at least 1 dose of study drug or placebo with evaluable PGE data at the specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 2 hr | -34.3 percentage change in PGE | Standard Deviation 20.1 |
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 144 hr | 178.2 percentage change in PGE | Standard Deviation 96.5 |
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 0.5 hours (hr) | -16.2 percentage change in PGE | Standard Deviation 32.9 |
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 1 hr | -9.2 percentage change in PGE | Standard Deviation 43.5 |
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 24 hr | 89.4 percentage change in PGE | Standard Deviation 153.9 |
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 8 hr | -8.5 percentage change in PGE | Standard Deviation 41 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 8 hr | -40.1 percentage change in PGE | Standard Deviation 25.4 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 2 hr | -45.5 percentage change in PGE | Standard Deviation 49.4 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 144 hr | 24.3 percentage change in PGE | Standard Deviation 58.2 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 1 hr | -4.8 percentage change in PGE | Standard Deviation 67.7 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 24 hr | 8.7 percentage change in PGE | Standard Deviation 73.3 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 0.5 hours (hr) | -15.6 percentage change in PGE | Standard Deviation 26.4 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 144 hr | 153.7 percentage change in PGE | Standard Deviation 70.9 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 24 hr | 60.0 percentage change in PGE | Standard Deviation 84.3 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 1 hr | 24.6 percentage change in PGE | Standard Deviation 67.5 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 0.5 hours (hr) | 33.0 percentage change in PGE | Standard Deviation 45 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 2 hr | -47.0 percentage change in PGE | Standard Deviation 19.8 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 8 hr | -41.3 percentage change in PGE | Standard Deviation 35.9 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 1 hr | -16.8 percentage change in PGE | Standard Deviation 93.7 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 0.5 hours (hr) | 12.7 percentage change in PGE | Standard Deviation 64 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 2 hr | -79.2 percentage change in PGE | Standard Deviation 21.2 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 8 hr | -79.3 percentage change in PGE | Standard Deviation 6.6 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 24 hr | -29.5 percentage change in PGE | — |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 144 hr | 131.1 percentage change in PGE | Standard Deviation 111.4 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 0.5 hours (hr) | 42.7 percentage change in PGE | Standard Deviation 69.7 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 24 hr | -76.8 percentage change in PGE | Standard Deviation 40.6 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 2 hr | -104.9 percentage change in PGE | Standard Deviation 11.8 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 8 hr | -94.3 percentage change in PGE | Standard Deviation 13.9 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 144 hr | 125.1 percentage change in PGE | Standard Deviation 104.6 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 1 hr | -83.8 percentage change in PGE | Standard Deviation 41.4 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 8 hr | -88.3 percentage change in PGE | Standard Deviation 13.5 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 2 hr | -96.4 percentage change in PGE | Standard Deviation 8.9 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 0.5 hours (hr) | -85.1 percentage change in PGE | Standard Deviation 13.8 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 24 hr | -54.1 percentage change in PGE | Standard Deviation 28.4 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 144 hr | 48.0 percentage change in PGE | Standard Deviation 49.3 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 1 hr | -92.9 percentage change in PGE | Standard Deviation 8.5 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 2 hr | -83.3 percentage change in PGE | Standard Deviation 11.8 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 1 hr | -93.7 percentage change in PGE | Standard Deviation 6.9 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 144 hr | 41.4 percentage change in PGE | Standard Deviation 101.1 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 8 hr | -98.4 percentage change in PGE | Standard Deviation 3.8 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 0.5 hours (hr) | -43.1 percentage change in PGE | Standard Deviation 17.8 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 24 hr | -88.8 percentage change in PGE | Standard Deviation 12.2 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 2 hr | 65.1 percentage change in PGE | Standard Deviation 106.6 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 24 hr | 124.8 percentage change in PGE | Standard Deviation 139.3 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 0.5 hours (hr) | 56.1 percentage change in PGE | Standard Deviation 97.9 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 8 hr | 76.9 percentage change in PGE | Standard Deviation 109.1 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 1 hr | 65.4 percentage change in PGE | Standard Deviation 116.8 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 144 hr | 159.1 percentage change in PGE | Standard Deviation 138.7 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 144 hr | 7.6 percentage change in PGE | Standard Deviation 76.5 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 2 hr | -68.2 percentage change in PGE | Standard Deviation 27.8 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 24 hr | -19.9 percentage change in PGE | Standard Deviation 60.7 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 0.5 hours (hr) | -10.4 percentage change in PGE | Standard Deviation 77.6 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 1 hr | -44.8 percentage change in PGE | Standard Deviation 59.5 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Ex Vivo Whole Blood Prostaglandin E (PGE) Synthesis After Lipopolysaccharide (LPS) Stimulation | 8 hr | -63.1 percentage change in PGE | Standard Deviation 32.1 |
Secondary
Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM)
The participant's urine was collected during protocol-defined intervals and the PGE metabolite PGIM was assessed. PGIM results for each interval were then compared to the baseline value.
Time frame: 0 to 2, 2 to 4, 4 to 6, and 6 to 12 hours post dose
Population: All participants who received at least 1 dose of study drug or placebo with evaluable PGIM data at specific time points
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 6 - 12 hr interval | 48.0 percentage change in PGIM | Standard Deviation 45.1 |
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 2 - 4 hr interval | 34.0 percentage change in PGIM | Standard Deviation 64.3 |
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 4 - 6 hr interval | 73.8 percentage change in PGIM | Standard Deviation 66.1 |
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 0 - 2 hr interval | 14.1 percentage change in PGIM | Standard Deviation 36.5 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 6 - 12 hr interval | 52.1 percentage change in PGIM | Standard Deviation 45.2 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 0 - 2 hr interval | 25.2 percentage change in PGIM | Standard Deviation 41.9 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 2 - 4 hr interval | 30.5 percentage change in PGIM | Standard Deviation 20.8 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 4 - 6 hr interval | 19.3 percentage change in PGIM | Standard Deviation 45.8 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 4 - 6 hr interval | 31.0 percentage change in PGIM | Standard Deviation 52 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 6 - 12 hr interval | 63.6 percentage change in PGIM | Standard Deviation 19.1 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 2 - 4 hr interval | 21.2 percentage change in PGIM | Standard Deviation 35.4 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 0 - 2 hr interval | -3.9 percentage change in PGIM | Standard Deviation 27.4 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 4 - 6 hr interval | 72.1 percentage change in PGIM | Standard Deviation 69.3 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 6 - 12 hr interval | 71.7 percentage change in PGIM | Standard Deviation 66.4 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 0 - 2 hr interval | 11.7 percentage change in PGIM | Standard Deviation 28 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 2 - 4 hr interval | 33.1 percentage change in PGIM | Standard Deviation 42.8 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 0 - 2 hr interval | 44.6 percentage change in PGIM | Standard Deviation 44.3 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 6 - 12 hr interval | 208.5 percentage change in PGIM | Standard Deviation 78.8 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 2 - 4 hr interval | 244.7 percentage change in PGIM | Standard Deviation 147.6 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 4 - 6 hr interval | 198.3 percentage change in PGIM | Standard Deviation 80 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 2 - 4 hr interval | 174.1 percentage change in PGIM | Standard Deviation 249 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 0 - 2 hr interval | 137.2 percentage change in PGIM | Standard Deviation 195.5 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 4 - 6 hr interval | 186.7 percentage change in PGIM | Standard Deviation 70.1 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 6 - 12 hr interval | 190.0 percentage change in PGIM | Standard Deviation 117.5 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 4 - 6 hr interval | 264.0 percentage change in PGIM | Standard Deviation 114.3 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 2 - 4 hr interval | 122.5 percentage change in PGIM | Standard Deviation 114.3 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 6 - 12 hr interval | 201.4 percentage change in PGIM | Standard Deviation 141.9 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 0 - 2 hr interval | 37.2 percentage change in PGIM | Standard Deviation 30.1 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 2 - 4 hr interval | 6.2 percentage change in PGIM | Standard Deviation 81.9 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 0 - 2 hr interval | -17.0 percentage change in PGIM | Standard Deviation 24.2 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 4 - 6 hr interval | 28.3 percentage change in PGIM | Standard Deviation 71.1 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 6 - 12 hr interval | 57.5 percentage change in PGIM | Standard Deviation 208.1 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 2 - 4 hr interval | -44.6 percentage change in PGIM | Standard Deviation 21.3 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 0 - 2 hr interval | -18.9 percentage change in PGIM | Standard Deviation 25.6 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 6 - 12 hr interval | -12.1 percentage change in PGIM | Standard Deviation 53.8 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostacyclin Metabolite (PGIM) | At 4 - 6 hr interval | -25.6 percentage change in PGIM | Standard Deviation 45.4 |
Secondary
Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM)
The participant's urine was collected during protocol-defined intervals and the PGE metabolite PGEM was assessed. PGEM results for each interval were then compared to the baseline value.
Time frame: 0 to 2, 2 to 4, 4 to 6, 6 to 12 and 12 to 24 hours post dose
Population: All participants who received at least 1 dose of study drug or placebo with evaluable PGEM data at specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 6 - 12 hr interval | 4.9 percentage change in PGEM | Standard Deviation 40.9 |
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 12 - 24 hr interval | 3.9 percentage change in PGEM | Standard Deviation 20.1 |
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 0 - 2 hr interval | 14.4 percentage change in PGEM | Standard Deviation 35.8 |
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 4 - 6 hr interval | -0.8 percentage change in PGEM | Standard Deviation 39.3 |
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 2 - 4 hr interval | 14.5 percentage change in PGEM | Standard Deviation 39.4 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 12 - 24 hr interval | -32.6 percentage change in PGEM | Standard Deviation 33.5 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 0 - 2 hr interval | 18.5 percentage change in PGEM | Standard Deviation 31.4 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 6 - 12 hr interval | -17.9 percentage change in PGEM | Standard Deviation 56.4 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 2 - 4 hr interval | -2.1 percentage change in PGEM | Standard Deviation 43.4 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 4 - 6 hr interval | -1.5 percentage change in PGEM | Standard Deviation 57.4 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 4 - 6 hr interval | -22.1 percentage change in PGEM | Standard Deviation 35.5 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 12 - 24 hr interval | -12.9 percentage change in PGEM | Standard Deviation 31 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 0 - 2 hr interval | 11.0 percentage change in PGEM | Standard Deviation 40.6 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 6 - 12 hr interval | -13.5 percentage change in PGEM | Standard Deviation 42.5 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 2 - 4 hr interval | 5.8 percentage change in PGEM | Standard Deviation 45.5 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 0 - 2 hr interval | -26.6 percentage change in PGEM | Standard Deviation 25.9 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 12 - 24 hr interval | -37.9 percentage change in PGEM | Standard Deviation 29.3 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 4 - 6 hr interval | -44.2 percentage change in PGEM | Standard Deviation 27.3 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 2 - 4 hr interval | -45.2 percentage change in PGEM | Standard Deviation 32.3 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 6 - 12 hr interval | -41.9 percentage change in PGEM | Standard Deviation 23.7 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 0 - 2 hr interval | 17.3 percentage change in PGEM | Standard Deviation 53.5 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 6 - 12 hr interval | -18.8 percentage change in PGEM | Standard Deviation 42.5 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 2 - 4 hr interval | 6.1 percentage change in PGEM | Standard Deviation 66.3 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 4 - 6 hr interval | -9.2 percentage change in PGEM | Standard Deviation 56.9 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 12 - 24 hr interval | -26.9 percentage change in PGEM | Standard Deviation 43.6 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 0 - 2 hr interval | 10.7 percentage change in PGEM | Standard Deviation 32.7 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 2 - 4 hr interval | 29.6 percentage change in PGEM | Standard Deviation 64.1 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 4 - 6 hr interval | 15.8 percentage change in PGEM | Standard Deviation 50.8 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 12 - 24 hr interval | -7.3 percentage change in PGEM | Standard Deviation 38.2 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 6 - 12 hr interval | -13.0 percentage change in PGEM | Standard Deviation 38 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 2 - 4 hr interval | -12.0 percentage change in PGEM | Standard Deviation 41.4 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 4 - 6 hr interval | -24.2 percentage change in PGEM | Standard Deviation 39.4 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 0 - 2 hr interval | -19.8 percentage change in PGEM | Standard Deviation 36.4 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 6 - 12 hr interval | -37.5 percentage change in PGEM | Standard Deviation 26.2 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 12 - 24 hr interval | -43.6 percentage change in PGEM | Standard Deviation 33.1 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 2 - 4 hr interval | 11.2 percentage change in PGEM | Standard Deviation 32.1 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 6 - 12 hr interval | 2.9 percentage change in PGEM | Standard Deviation 44 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 12 - 24 hr interval | 0.9 percentage change in PGEM | Standard Deviation 32.8 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 4 - 6 hr interval | 6.3 percentage change in PGEM | Standard Deviation 44.4 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 0 - 2 hr interval | 5.8 percentage change in PGEM | Standard Deviation 47.3 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 0 - 2 hr interval | -14.6 percentage change in PGEM | Standard Deviation 40.7 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 2 - 4 hr interval | -30.7 percentage change in PGEM | Standard Deviation 36.1 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 6 - 12 hr interval | -36.8 percentage change in PGEM | Standard Deviation 27.9 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 4 - 6 hr interval | -32.3 percentage change in PGEM | Standard Deviation 42.4 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Prostaglandin E(2) Metabolite (PGEM) | 12 - 24 hr interval | -46.5 percentage change in PGEM | Standard Deviation 17.8 |
Secondary
Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM)
The participant's urine was collected during protocol-defined intervals and the PGE metabolite TXAM was assessed. TXAM results for each interval were then compared to the baseline value.
Time frame: 0 to 2, 2 to 4, 4 to 6, and 6 to 12 hours post dose
Population: All participants who received at least 1 dose of study drug or placebo with evaluable TXAM data at specific time points.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 4 - 6 hr interval | 1.3 percentage change in TXAM | Standard Deviation 25.4 |
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 6 - 12 hr interval | 6.8 percentage change in TXAM | Standard Deviation 29.5 |
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 2 - 4 hr interval | 4.1 percentage change in TXAM | Standard Deviation 16.1 |
| 5 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 0 - 2 hr interval | -9.0 percentage change in TXAM | Standard Deviation 10.2 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 0 - 2 hr interval | -5.7 percentage change in TXAM | Standard Deviation 9.6 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 6 - 12 hr interval | -15.7 percentage change in TXAM | Standard Deviation 19.6 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 2 - 4 hr interval | -15.5 percentage change in TXAM | Standard Deviation 7.7 |
| 25 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 4 - 6 hr interval | -16.5 percentage change in TXAM | Standard Deviation 11.4 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 2 - 4 hr interval | 19.7 percentage change in TXAM | Standard Deviation 23.7 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 0 - 2 hr interval | 0.9 percentage change in TXAM | Standard Deviation 17.4 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 6 - 12 hr interval | 20.7 percentage change in TXAM | Standard Deviation 23.2 |
| 75 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 4 - 6 hr interval | 1.2 percentage change in TXAM | Standard Deviation 16.9 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 2 - 4 hr interval | 0.7 percentage change in TXAM | Standard Deviation 22.1 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 0 - 2 hr interval | -11.3 percentage change in TXAM | Standard Deviation 10.8 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 6 - 12 hr interval | 8.0 percentage change in TXAM | Standard Deviation 25.2 |
| 225 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 4 - 6 hr interval | -3.8 percentage change in TXAM | Standard Deviation 16.4 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 4 - 6 hr interval | 29.4 percentage change in TXAM | Standard Deviation 29.6 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 0 - 2 hr interval | 4.4 percentage change in TXAM | Standard Deviation 13.8 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 2 - 4 hr interval | 40.4 percentage change in TXAM | Standard Deviation 52.4 |
| 450 mg LY3031207 Fed | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 6 - 12 hr interval | 30.9 percentage change in TXAM | Standard Deviation 29.6 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 0 - 2 hr interval | 25.2 percentage change in TXAM | Standard Deviation 31.5 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 6 - 12 hr interval | 9.0 percentage change in TXAM | Standard Deviation 23.1 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 2 - 4 hr interval | 28.3 percentage change in TXAM | Standard Deviation 58.3 |
| 450 mg LY3031207 Fasted | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 4 - 6 hr interval | 16.7 percentage change in TXAM | Standard Deviation 25.2 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 6 - 12 hr interval | 85.8 percentage change in TXAM | Standard Deviation 85.9 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 2 - 4 hr interval | 106.2 percentage change in TXAM | Standard Deviation 107.1 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 4 - 6 hr interval | 88.5 percentage change in TXAM | Standard Deviation 47.9 |
| 900 mg LY3031207 | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 0 - 2 hr interval | 11.0 percentage change in TXAM | Standard Deviation 24.7 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 2 - 4 hr interval | -17.4 percentage change in TXAM | Standard Deviation 17.2 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 0 - 2 hr interval | -11.5 percentage change in TXAM | Standard Deviation 22.6 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 6 - 12 hr interval | 13.1 percentage change in TXAM | Standard Deviation 14.8 |
| Placebo | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 4 - 6 hr interval | -18.3 percentage change in TXAM | Standard Deviation 18.7 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 4 - 6 hr interval | -33.3 percentage change in TXAM | Standard Deviation 10.6 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 2 - 4 hr interval | -25.4 percentage change in TXAM | Standard Deviation 17 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 0 - 2 hr interval | -6.2 percentage change in TXAM | Standard Deviation 19.3 |
| 400 mg Celecoxib | Pharmacodynamics: Percent Change From Baseline of Urinary Excretion of Thromboxane A Metabolite (TXAM) | At 6 - 12 hr interval | -19.8 percentage change in TXAM | Standard Deviation 18.3 |
Secondary
Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of LY3031207
AUC from time 0 to last timepoint (AUC0-tlast) with measurable concentration of LY3031207.
Time frame: Predose, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 96, 144 hours post dose
Population: Pharmacokinetic (PK) population: All participants who received at least 1 dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg LY3031207 | Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of LY3031207 | 3040 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 31 |
| 25 mg LY3031207 | Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of LY3031207 | 13900 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 65 |
| 75 mg LY3031207 | Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of LY3031207 | 40000 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 32 |
| 225 mg LY3031207 | Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of LY3031207 | 151000 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 28 |
| 450 mg LY3031207 Fed | Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of LY3031207 | 171000 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 54 |
| 450 mg LY3031207 Fasted | Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of LY3031207 | 116000 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 73 |
| 900 mg LY3031207 | Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of LY3031207 | 348000 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 63 |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207
Time frame: Predose, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 96, 144 hours post dose
Population: Pharmacokinetic (PK) population: all participants who received at least one dose of study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg LY3031207 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207 | 185 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35 |
| 25 mg LY3031207 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207 | 818 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 40 |
| 75 mg LY3031207 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207 | 2060 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 20 |
| 225 mg LY3031207 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207 | 5610 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 31 |
| 450 mg LY3031207 Fed | Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207 | 7780 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 32 |
| 450 mg LY3031207 Fasted | Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207 | 5670 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49 |
| 900 mg LY3031207 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207 | 11300 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 45 |