Healthy Volunteers
Conditions
Brief summary
This is a study of LY3023703 in healthy participants. The purposes of this study are to look at safety, how well the study drug is tolerated, how much of the study drug gets into the blood stream and how long it takes the body to remove the study drug. The effects of LY3023703 on blood pressure after 28 days of dosing will be studied. Information about any side effects that occur will be collected. The study is expected to last 21 weeks.
Interventions
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Overtly healthy individuals based on the history and physical examinations as determined by the investigator * Are normotensive (defined as supine systolic blood pressure \[BP\] less than 140 millimeters of mercury \[mm Hg\] and diastolic BP less than 90 mm Hg without the use of any antihypertensives) or results that are judged to be not clinically significant by the investigator
Exclusion criteria
* Have presence of clinically significant active bleeding or history of bleeding diathesis at the time of screening * Have presence of active peptic ulcer disease, gastro-intestinal (GI) bleeding, chronic gastritis, inflammatory bowel disease, or chronic diarrhea * Have evidence of other chronic liver disease * Have any use of nonsteroidal anti-inflammatory drugs (NSAIDs), celecoxib, aspirin, or acetaminophen (at doses greater than 1 gram per day \[g/day\] within 14 days of admission * Have greater than 1 plus pretibial pitting edema or 2 plus ankle or pedal edema
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | Baseline to Study Completion (up to 74 Days) | A summary of serious and all other non-serious adverse events (AE), regardless of possible study drug relatedness, is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve [AUC(0-24)] of LY3023703 | Post-First Dose on Days 1-28 (Time Frame: Day 1: -0.5, 1, 2, 4, 8, 12, 24 hours; Days 5, 12, 20: -0.5 hours; Day 28: -0.5, 1, 2, 4, 8, 12, 24 hours.) | — |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 | Post first dose on Day 1 through Day 28 (Time Frame: Day 1: -0.5, 1, 2, 4, 8, 12, 24 hours; Days 5, 12, 20: -0.5 hours; Day 28: -0.5, 1, 2, 4, 8, 12, 24 hours.) | — |
| Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3023703 | Post first dose on Day 1 through Day 28 (Time Frame: Day 1: -0.5, 1, 2, 4, 8, 12, 24 hours; Days 5, 12, 20: -0.5 hours; Day 28: -0.5, 1, 2, 4, 8, 12, 24 hours.) | — |
| Change From Baseline to Day 27 in Blood Pressure (BP) | Baseline, Day 27 | The Day 27 change from Day -1 was analyzed by using analysis of covariance (ANCOVA) with treatment as a fixed effect and baseline Day -1 as a covariate. The treatment mean, difference to placebo, and difference to celecoxib were output with corresponding 90% confidence intervals. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo administered PO, QD, for 28 days | 8 |
| 2.5 mg LY3023703 2.5 mg LY3023703 administered PO, QD, for 28 days | 8 |
| 7.5 mg LY3023703 7.5 mg LY3023703 administered PO, QD, for 28 days | 8 |
| 15 mg LY3023703 15 mg LY3023703 administered PO, QD, for 28 days | 8 |
| 30 mg LY3023703 30 mg LY3023703 administered PO, QD, for 28 days | 8 |
| 400 mg Celecoxib 400 mg celecoxib administered PO, QD, for 28 days | 8 |
| Total | 48 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 400 mg Celecoxib | Total | Placebo | 2.5 mg LY3023703 | 7.5 mg LY3023703 | 15 mg LY3023703 | 30 mg LY3023703 |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 39.1 Years STANDARD_DEVIATION 6.8 | 39.7 Years STANDARD_DEVIATION 9.8 | 37.8 Years STANDARD_DEVIATION 10.6 | 43.0 Years STANDARD_DEVIATION 11.7 | 37.9 Years STANDARD_DEVIATION 12.6 | 41.4 Years STANDARD_DEVIATION 10.4 | 39.0 Years STANDARD_DEVIATION 7.7 |
| Race/Ethnicity, Customized American Indian/Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Black/African American | 5 Participants | 18 Participants | 3 Participants | 2 Participants | 3 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 3 Participants | 25 Participants | 5 Participants | 6 Participants | 4 Participants | 4 Participants | 3 Participants |
| Region of Enrollment United States | 8 Participants | 48 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants | 8 Participants |
| Sex: Female, Male Female | 1 Participants | 7 Participants | 1 Participants | 3 Participants | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 7 Participants | 41 Participants | 7 Participants | 5 Participants | 7 Participants | 8 Participants | 7 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 8 | 3 / 8 | 3 / 8 | 4 / 8 | 5 / 8 | 3 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
A summary of serious and all other non-serious adverse events (AE), regardless of possible study drug relatedness, is located in the Reported Adverse Events module.
Time frame: Baseline to Study Completion (up to 74 Days)
Population: Randomized participants who reported an AE that met any of the serious criteria.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 2.5 mg LY3023703 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 7.5 mg LY3023703 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 15 mg LY3023703 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 30 mg LY3023703 | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
| 400 mg Celecoxib | Number of Participants With One or More Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration | 0 Participants |
Secondary
Change From Baseline to Day 27 in Blood Pressure (BP)
The Day 27 change from Day -1 was analyzed by using analysis of covariance (ANCOVA) with treatment as a fixed effect and baseline Day -1 as a covariate. The treatment mean, difference to placebo, and difference to celecoxib were output with corresponding 90% confidence intervals.
Time frame: Baseline, Day 27
Population: All randomized participants who received at least one dose of study treatment and had evaluable data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Placebo | Change From Baseline to Day 27 in Blood Pressure (BP) | Diastolic Blood Pressure (DBP) | 0.28 millimeters of mercury (mmHg) |
| Placebo | Change From Baseline to Day 27 in Blood Pressure (BP) | Systolic Blood Pressure (SBP) | -1.45 millimeters of mercury (mmHg) |
| 2.5 mg LY3023703 | Change From Baseline to Day 27 in Blood Pressure (BP) | Systolic Blood Pressure (SBP) | -2.67 millimeters of mercury (mmHg) |
| 2.5 mg LY3023703 | Change From Baseline to Day 27 in Blood Pressure (BP) | Diastolic Blood Pressure (DBP) | -0.11 millimeters of mercury (mmHg) |
| 7.5 mg LY3023703 | Change From Baseline to Day 27 in Blood Pressure (BP) | Diastolic Blood Pressure (DBP) | -0.83 millimeters of mercury (mmHg) |
| 7.5 mg LY3023703 | Change From Baseline to Day 27 in Blood Pressure (BP) | Systolic Blood Pressure (SBP) | -2.54 millimeters of mercury (mmHg) |
| 15 mg LY3023703 | Change From Baseline to Day 27 in Blood Pressure (BP) | Systolic Blood Pressure (SBP) | -2.99 millimeters of mercury (mmHg) |
| 15 mg LY3023703 | Change From Baseline to Day 27 in Blood Pressure (BP) | Diastolic Blood Pressure (DBP) | -0.68 millimeters of mercury (mmHg) |
| 30 mg LY3023703 | Change From Baseline to Day 27 in Blood Pressure (BP) | Diastolic Blood Pressure (DBP) | -1.22 millimeters of mercury (mmHg) |
| 30 mg LY3023703 | Change From Baseline to Day 27 in Blood Pressure (BP) | Systolic Blood Pressure (SBP) | -2.98 millimeters of mercury (mmHg) |
| 400 mg Celecoxib | Change From Baseline to Day 27 in Blood Pressure (BP) | Diastolic Blood Pressure (DBP) | -2.24 millimeters of mercury (mmHg) |
| 400 mg Celecoxib | Change From Baseline to Day 27 in Blood Pressure (BP) | Systolic Blood Pressure (SBP) | -5.29 millimeters of mercury (mmHg) |
Comparison: SBP90% CI: [-4.98, 2.54]
Comparison: SBP90% CI: [-4.7, 2.53]
Comparison: SBP90% CI: [-5.3, 2.22]
Comparison: SBP90% CI: [-5.16, 2.1]
Comparison: SBP90% CI: [-7.74, 0.07]
Comparison: DBP90% CI: [-2.95, 2.18]
Comparison: DBP90% CI: [-3.69, 1.48]
Comparison: DBP90% CI: [-3.75, 1.85]
Comparison: DBP90% CI: [-4.09, 1.1]
Comparison: DBP90% CI: [-5.23, 0.2]
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703
Time frame: Post first dose on Day 1 through Day 28 (Time Frame: Day 1: -0.5, 1, 2, 4, 8, 12, 24 hours; Days 5, 12, 20: -0.5 hours; Day 28: -0.5, 1, 2, 4, 8, 12, 24 hours.)
Population: All randomized participants who received at least one dose of the study medication and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 | Single Oral Dose (Day 1) | 42.6 ng/mL | Geometric Coefficient of Variation 25.2 |
| Placebo | Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 | Multiple Oral Doses (Day 28) | 41.9 ng/mL | Geometric Coefficient of Variation 47.5 |
| 2.5 mg LY3023703 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 | Multiple Oral Doses (Day 28) | 151 ng/mL | Geometric Coefficient of Variation 47 |
| 2.5 mg LY3023703 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 | Single Oral Dose (Day 1) | 126 ng/mL | Geometric Coefficient of Variation 35.2 |
| 7.5 mg LY3023703 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 | Single Oral Dose (Day 1) | 228 ng/mL | Geometric Coefficient of Variation 25.6 |
| 7.5 mg LY3023703 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 | Multiple Oral Doses (Day 28) | 243 ng/mL | Geometric Coefficient of Variation 28.3 |
| 15 mg LY3023703 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 | Single Oral Dose (Day 1) | 556 ng/mL | Geometric Coefficient of Variation 30.1 |
| 15 mg LY3023703 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3023703 | Multiple Oral Doses (Day 28) | 711 ng/mL | Geometric Coefficient of Variation 26.2 |
Secondary
Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve [AUC(0-24)] of LY3023703
Time frame: Post-First Dose on Days 1-28 (Time Frame: Day 1: -0.5, 1, 2, 4, 8, 12, 24 hours; Days 5, 12, 20: -0.5 hours; Day 28: -0.5, 1, 2, 4, 8, 12, 24 hours.)
Population: All randomized participants who received at least one dose of the study medication and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve [AUC(0-24)] of LY3023703 | Single Oral Dose (Day 1) | 332 hours•nanogram/milliliter (hr•ng/mL) | Geometric Coefficient of Variation 41.4 |
| Placebo | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve [AUC(0-24)] of LY3023703 | Multiple Oral Doses (Day 28) | 300 hours•nanogram/milliliter (hr•ng/mL) | Geometric Coefficient of Variation 39.3 |
| 2.5 mg LY3023703 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve [AUC(0-24)] of LY3023703 | Multiple Oral Doses (Day 28) | 1340 hours•nanogram/milliliter (hr•ng/mL) | Geometric Coefficient of Variation 43.7 |
| 2.5 mg LY3023703 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve [AUC(0-24)] of LY3023703 | Single Oral Dose (Day 1) | 1140 hours•nanogram/milliliter (hr•ng/mL) | Geometric Coefficient of Variation 31.7 |
| 7.5 mg LY3023703 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve [AUC(0-24)] of LY3023703 | Single Oral Dose (Day 1) | 2300 hours•nanogram/milliliter (hr•ng/mL) | Geometric Coefficient of Variation 12.4 |
| 7.5 mg LY3023703 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve [AUC(0-24)] of LY3023703 | Multiple Oral Doses (Day 28) | 2880 hours•nanogram/milliliter (hr•ng/mL) | Geometric Coefficient of Variation 19.2 |
| 15 mg LY3023703 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve [AUC(0-24)] of LY3023703 | Single Oral Dose (Day 1) | 5290 hours•nanogram/milliliter (hr•ng/mL) | Geometric Coefficient of Variation 24 |
| 15 mg LY3023703 | Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve [AUC(0-24)] of LY3023703 | Multiple Oral Doses (Day 28) | 8520 hours•nanogram/milliliter (hr•ng/mL) | Geometric Coefficient of Variation 24.7 |
Secondary
Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3023703
Time frame: Post first dose on Day 1 through Day 28 (Time Frame: Day 1: -0.5, 1, 2, 4, 8, 12, 24 hours; Days 5, 12, 20: -0.5 hours; Day 28: -0.5, 1, 2, 4, 8, 12, 24 hours.)
Population: All randomly assigned participants who received at least one dose of the study medication and had evaluable PK data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Placebo | Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3023703 | Single Oral Dose (Day 1) | 2.01 Hours |
| Placebo | Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3023703 | Multiple Oral Doses (Day 28) | 2.00 Hours |
| 2.5 mg LY3023703 | Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3023703 | Multiple Oral Doses (Day 28) | 2.00 Hours |
| 2.5 mg LY3023703 | Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3023703 | Single Oral Dose (Day 1) | 3.00 Hours |
| 7.5 mg LY3023703 | Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3023703 | Single Oral Dose (Day 1) | 4.00 Hours |
| 7.5 mg LY3023703 | Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3023703 | Multiple Oral Doses (Day 28) | 4.00 Hours |
| 15 mg LY3023703 | Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3023703 | Single Oral Dose (Day 1) | 4.00 Hours |
| 15 mg LY3023703 | Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3023703 | Multiple Oral Doses (Day 28) | 4.00 Hours |