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| ID | Type | Description | Link |
|---|---|---|---|
| I5W-EW-LBCA | Other Identifier | Eli Lilly and Company |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LY3031207 | Experimental | Participants received escalating doses of 5 mg (milligrams), 25 mg, 75 mg, 225 mg, 450 mg and 900 mg of LY3031207 capsule orally. |
|
| Placebo | Placebo Comparator | Single dose of placebo administered orally in up to two occasions separated by at least a 3 week wash-out period between each dose. |
|
| Celecoxib | Active Comparator | Single 400mg dose of celecoxib administered orally on one occasion. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LY3031207 | Drug | Administered orally |
| |
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline, up to 4 months |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics: Area Under the Concentration-Time Curve (AUC) of LY3031207 | AUC from time 0 to last timepoint (AUC0-tlast) with measurable concentration of LY3031207. | Predose, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 96, 144 hours post dose |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri, 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician. | Evansville | Indiana | 47710 |
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| FG002 | 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 |
| FG003 | 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 |
| FG004 | 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) |
| FG005 | 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) |
| FG006 | 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 |
| FG007 | 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 |
| FG008 | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1 |
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| Period 2 |
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| Period 3 |
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All randomized participants who received study drug.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Cohort I Sequence 2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | All participants who received at least 1 dose of study drug or placebo. | Posted | Count of Participants | Participants | No | Baseline, up to 4 months |
|
Up To 4 Months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 5 mg LY3031207 | 5 mg LY3031207 administered orally as capsules as a single dose. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 14.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | Eli Lilly and Company | 800-545-5979 |
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| ID | Term |
|---|---|
| C000627901 | LY3031207 |
| D000068579 | Celecoxib |
| ID | Term |
|---|---|
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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| Drug |
Administered orally |
|
| Celecoxib | Drug | Administered orally |
|
| 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 | The effect of LY3031207 on PGE synthesis in whole blood after ex vivo LPS stimulation. | Predose, 0.5, 1, 2, 8, 24 and 144 hours post dose. |
| 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. | 0 to 2, 2 to 4, 4 to 6, 6 to 12 and 12 to 24 hours post dose |
| 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. | 0 to 2, 2 to 4, 4 to 6, and 6 to 12 hours post dose |
| 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. | 0 to 2, 2 to 4, 4 to 6, and 6 to 12 hours post dose |
| United States |
| Sponsor Decision |
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| COMPLETED |
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| NOT COMPLETED |
|
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| COMPLETED |
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| NOT COMPLETED |
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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
| BG002 | 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 |
| BG003 | 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 |
| BG004 | 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) |
| BG005 | 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) |
| BG006 | 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 |
| BG007 | 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 |
| BG008 | 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 |
| BG009 | Total | Total of all reporting groups |
| Participants |
| No |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Race/Ethnicity, Customized | Count of Participants | Participants | No |
|
| Region of Enrollment | Count of Participants | Participants | No |
|
| OG002 | 75 mg LY3031207 | 75 mg LY3031207 administered orally as capsules as a single dose. |
| OG003 | 225 mg LY3031207 | 225 mg LY3031207 administered orally as capsules as a single dose. |
| OG004 | 450 mg LY3031207 Fed | 450 mg LY3031207 administered orally as capsules as a single dose. |
| OG005 | 450 mg LY3031207 Fasted | 450 mg LY3031207 administered orally as capsules as a single dose to participants who were fasted. |
| OG006 | 900 mg LY3031207 | 900 mg LY3031207 administered orally as capsules as a single dose. |
| OG007 | Placebo | Matched placebo capsules administered orally. |
| OG008 | 400 mg Celecoxib | 400 mg Celecoxib administered orally as capsules. |
|
|
| 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. | Pharmacokinetic (PK) population: All participants who received at least 1 dose of study drug and had evaluable PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng*hr/mL) | Predose, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 96, 144 hours post dose |
|
|
|
| Secondary | Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207 | Pharmacokinetic (PK) population: all participants who received at least one dose of study drug and had evaluable PK data. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Predose, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 96, 144 hours post dose |
|
|
|
| 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. | All participants who received at least 1 dose of study drug or placebo with evaluable PGE data at the specific time points. | Posted | Mean | Standard Deviation | percentage change in PGE | Predose, 0.5, 1, 2, 8, 24 and 144 hours post dose. |
|
|
|
| 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. | All participants who received at least 1 dose of study drug or placebo with evaluable PGEM data at specific time points. | Posted | Mean | Standard Deviation | percentage change in PGEM | 0 to 2, 2 to 4, 4 to 6, 6 to 12 and 12 to 24 hours post dose |
|
|
|
| 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. | All participants who received at least 1 dose of study drug or placebo with evaluable PGIM data at specific time points | Posted | Mean | Standard Deviation | percentage change in PGIM | 0 to 2, 2 to 4, 4 to 6, and 6 to 12 hours post dose |
|
|
|
| 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. | All participants who received at least 1 dose of study drug or placebo with evaluable TXAM data at specific time points. | Posted | Mean | Standard Deviation | percentage change in TXAM | 0 to 2, 2 to 4, 4 to 6, and 6 to 12 hours post dose |
|
|
|
| 0 |
| 8 |
| 3 |
| 8 |
| EG001 | 25 mg LY3031207 | 25 mg LY3031207 administered orally as capsules as a single dose. | 0 | 6 | 3 | 6 |
| EG002 | 75 mg LY3031207 | 75 mg LY3031207 administered orally as capsules as a single dose. | 0 | 8 | 1 | 8 |
| EG003 | 225 mg LY3031207 | 225 mg LY3031207 administered orally as capsules as a single dose. | 0 | 7 | 1 | 7 |
| EG004 | 450 mg LY3031207 Fed | 450 mg LY3031207 administered orally as capsules as a single dose. | 0 | 6 | 0 | 6 |
| EG005 | 450 mg LY3031207 Fasted | 450 mg LY3031207 administered orally as capsules as a single dose to participants who were fasted before receiving drug. | 0 | 6 | 2 | 6 |
| EG006 | 900 mg LY3031207 | 900 mg LY3031207 administered orally as capsules as a single dose. | 0 | 8 | 2 | 8 |
| EG007 | Placebo | Matched placebo capsules administered orally. | 0 | 10 | 2 | 10 |
| EG008 | 400 mg Celecoxib | 400 mg Celecoxib administered orally as capsules. | 0 | 18 | 1 | 18 |
| Photophobia | Eye disorders | MedDRA 14.0 | Systematic Assessment |
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| Visual impairment | Eye disorders | MedDRA 14.0 | Systematic Assessment |
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| Abdominal distension | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA 14.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 14.0 | Systematic Assessment |
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| Vessel puncture site haematoma | General disorders | MedDRA 14.0 | Systematic Assessment |
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| Gingival infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA 14.0 | Systematic Assessment |
|
| Concussion | Injury, poisoning and procedural complications | MedDRA 14.0 | Systematic Assessment |
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| Weight increased | Investigations | MedDRA 14.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 14.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
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| Loss of consciousness | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Tremor | Nervous system disorders | MedDRA 14.0 | Systematic Assessment |
|
| Testicular pain | Reproductive system and breast disorders | MedDRA 14.0 | Systematic Assessment |
|
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| D001555 |
| Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011720 | Pyrazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| 1 hr |
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| 2 hr |
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| 8 hr |
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| 24 hr |
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| 144 hr |
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| 2 - 4 hr interval |
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| 4 - 6 hr interval |
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| 6 - 12 hr interval |
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| 12 - 24 hr interval |
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| At 2 - 4 hr interval |
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| At 4 - 6 hr interval |
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| At 6 - 12 hr interval |
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| At 2 - 4 hr interval |
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| At 4 - 6 hr interval |
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| At 6 - 12 hr interval |
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