Healthy Volunteers
Conditions
Brief summary
The purposes of this study are to look at safety, how well the study drug is tolerated, how much of the study drug gets into the blood stream, and how long it takes the body to get rid of it when given to healthy Japanese and non-Japanese participants as multiple doses. In addition, effects of 28-day oral dosing of LY3031207 on the amount of a cholesterol-lowering drug (simvastatin) that gets into the blood stream and how long the body takes to get rid of it will be determined. The effects of LY3031207 after single and 28-day dosing on blood pressure will also be studied. Information about any side effects that may occur will be collected.
Interventions
DRUGPlacebo
Capsules administered orally
DRUGLY3031207
Administered orally
DRUGCelecoxib
Administered orally
DRUGSimvastatin
Administered orally
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, including first generation Japanese * Body mass index between 17.0 and 32.0 kilograms per square meter (kg/m\^2), inclusive
Exclusion criteria
* Have known allergies to LY3031207 or any components of the formulation, simvastatin or related compounds (other 3-Hydroxy-3-Methyl-Glutaryl-CoA \[HMG CoA\] reductase inhibitors), celecoxib, or sulfonamides. Participants with known aspirin allergy or allergic reaction to nonsteroidal anti-inflammatory drugs (NSAIDs) should also be excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs | Baseline to study completion (treatment completion and follow-up, up to 35 weeks) | A treatment emergent adverse event (TEAE) is defined as an adverse event (AE) that occurs postdose or that is present predose and becomes more severe postdose. AEs presented are of all causalities and all severities. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Day 28 in Urinary Thromboxane A (TXA) Metabolite Excretion | Baseline, Predose up to 12 hours prior to last dose at Day 28 | — |
| Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207 | Predose up to 48 hours post last dose at Day 28 | Maximum concentration (Cmax) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm. |
| Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3031207 | Predose up to 48 hours post last dose at Day 28 | Area under the concentration versus time curve in a dosing interval (AUC\[0-tau\]) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm. |
| Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3031207 | Predose up to 48 hours post last dose at Day 28 | Time of maximum concentration (Tmax) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm. |
| Change From Baseline to Day 28 in Urinary Prostaglandin E (PGE) Metabolite Excretion | Baseline, Predose up to time of last dose at Day 28 | — |
| Pharmacokinetics: Area Under the Concentration Curve (AUC) of Simvastatin | Predose up to 48 hours post dose at Day -3 and Day 28 | Area under the concentration versus time curve over the range of all measureable concentrations (AUC\[0-tlast\]) of simvastatin. |
| Pharmacokinetics: Time of Maximum Concentration (Tmax) of Simvastatin | Predose up to 48 hours post dose at Day -3 and Day 28 | — |
| Change From Baseline to Day 28 in Urinary Prostacyclin I (PGI) Metabolite Excretion | Baseline, Predose up to 12 hours prior to last dose at Day 28 | — |
| Pharmacokinetics: Maximum Concentration (Cmax) of Simvastatin | Predose up to 48 hours post dose at Day -3 and Day 28 | — |
Countries
United States
Participant flow
Pre-assignment details
Study enrolled participants of both Japanese and non-Japanese decent. Participants were pooled regardless of ethnicity. Participants assigned to 75 milligrams (mg) LY3031207 and 225 mg LY3031207 underwent identical procedures as those assigned to 25 mg LY3031207 with the addition of 10 mg open-label simvastatin administration on Days -3 and 28.
Participants by arm
| Arm | Count |
|---|---|
| 25 mg LY3031207 Daily oral administration of 25 milligrams (mg) LY3031207 for 28 days. | 8 |
| 75 mg LY3031207 and Simvastatin Daily oral administration of 75 mg LY3031207 for up to 28 days. In addition, participants received oral administration of 10 mg open-label simvastatin on Days -3 and 28. | 10 |
| 225 mg LY3031207 and Simvastatin Daily oral administration of 225 mg LY3031207 for up to 22 days. In addition, participants received oral administration of 10 mg open-label simvastatin on Day -3 only. | 9 |
| Placebo With or Without Simvastatin Daily oral administration of placebo for up to 28 days with or without oral administration of 10 mg open-label simvastatin on Days -3 and 28. | 6 |
| 400 mg Celecoxib With or Without Simvastatin Daily oral administration of 400 mg celecoxib for up to 28 days with or without oral administration of 10 mg open-label simvastatin on Days -3 and 28. | 6 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Sponsor Decision | 0 | 2 | 9 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 25 mg LY3031207 | Total | 400 mg Celecoxib With or Without Simvastatin | Placebo With or Without Simvastatin | 225 mg LY3031207 and Simvastatin | 75 mg LY3031207 and Simvastatin |
|---|---|---|---|---|---|---|
| Age, Continuous | 37.8 years STANDARD_DEVIATION 11.8 | 43.0 years STANDARD_DEVIATION 11.9 | 44.0 years STANDARD_DEVIATION 7.8 | 52.7 years STANDARD_DEVIATION 5.8 | 45.1 years STANDARD_DEVIATION 14.7 | 39.0 years STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 38 Participants | 6 Participants | 6 Participants | 9 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 12 Participants | 2 Participants | 3 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 7 Participants | 0 Participants | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 20 Participants | 4 Participants | 2 Participants | 3 Participants | 6 Participants |
| Region of Enrollment United States | 8 Participants | 39 Participants | 6 Participants | 6 Participants | 9 Participants | 10 Participants |
| Sex: Female, Male Female | 1 Participants | 9 Participants | 0 Participants | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 7 Participants | 30 Participants | 6 Participants | 4 Participants | 5 Participants | 8 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 | 1 / 6 | 3 / 8 | 5 / 10 | 9 / 9 | 1 / 6 | 3 / 27 |
| serious Total, serious adverse events | 0 / 6 | 0 / 8 | 0 / 10 | 2 / 9 | 0 / 6 | 0 / 27 |
Outcome results
Primary
Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs
A treatment emergent adverse event (TEAE) is defined as an adverse event (AE) that occurs postdose or that is present predose and becomes more severe postdose. AEs presented are of all causalities and all severities. A summary of serious and other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Time frame: Baseline to study completion (treatment completion and follow-up, up to 35 weeks)
Population: Participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 25 mg LY3031207 | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs | Participants with one or more AEs | 3 Participants |
| 25 mg LY3031207 | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs | Participants with one or more serious AEs | 0 Participants |
| 75 mg LY3031207 and Simvastatin | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs | Participants with one or more AEs | 5 Participants |
| 75 mg LY3031207 and Simvastatin | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs | Participants with one or more serious AEs | 0 Participants |
| 225 mg LY3031207 and Simvastatin | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs | Participants with one or more AEs | 9 Participants |
| 225 mg LY3031207 and Simvastatin | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs | Participants with one or more serious AEs | 2 Participants |
| Placebo With or Without Simvastatin | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs | Participants with one or more AEs | 1 Participants |
| Placebo With or Without Simvastatin | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs | Participants with one or more serious AEs | 0 Participants |
| 400 mg Celecoxib With or Without Simvastatin | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs | Participants with one or more AEs | 1 Participants |
| 400 mg Celecoxib With or Without Simvastatin | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs | Participants with one or more serious AEs | 0 Participants |
| 10 mg Simvastatin | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs | Participants with one or more AEs | 3 Participants |
| 10 mg Simvastatin | Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs | Participants with one or more serious AEs | 0 Participants |
Secondary
Change From Baseline to Day 28 in Urinary Prostacyclin I (PGI) Metabolite Excretion
Time frame: Baseline, Predose up to 12 hours prior to last dose at Day 28
Population: Zero participants were analyzed. Data not collected.
Secondary
Change From Baseline to Day 28 in Urinary Prostaglandin E (PGE) Metabolite Excretion
Time frame: Baseline, Predose up to time of last dose at Day 28
Population: Zero participants were analyzed. Data not collected.
Secondary
Change From Baseline to Day 28 in Urinary Thromboxane A (TXA) Metabolite Excretion
Time frame: Baseline, Predose up to 12 hours prior to last dose at Day 28
Population: Zero participants were analyzed. Data not collected.
Secondary
Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3031207
Area under the concentration versus time curve in a dosing interval (AUC\[0-tau\]) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm.
Time frame: Predose up to 48 hours post last dose at Day 28
Population: Participants who received at least one dose of LY3031207 with evaluable AUC (0-tau) data at Day 28. Participants who had incomplete data due to early discontinuation were not analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 25 mg LY3031207 | Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3031207 | 12000 nanograms*hours/milliliter (hr*ng/mL) | Geometric Coefficient of Variation 39.7 |
| 75 mg LY3031207 and Simvastatin | Pharmacokinetics: Area Under the Concentration Curve (AUC) of LY3031207 | 30400 nanograms*hours/milliliter (hr*ng/mL) | Geometric Coefficient of Variation 45 |
Secondary
Pharmacokinetics: Area Under the Concentration Curve (AUC) of Simvastatin
Area under the concentration versus time curve over the range of all measureable concentrations (AUC\[0-tlast\]) of simvastatin.
Time frame: Predose up to 48 hours post dose at Day -3 and Day 28
Population: Participants dosed with 75 mg LY3031207 from Days 1 through 28 and with oral administration of 10 mg open-label simvastatin on Days -3 and 28 and who had complete pharmacokinetic profiles following both simvastatin dosing events. Participants who had incomplete data due to early discontinuation were not analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 25 mg LY3031207 | Pharmacokinetics: Area Under the Concentration Curve (AUC) of Simvastatin | 5.23 nanograms*hours/milliliter (hr*ng/mL) | Geometric Coefficient of Variation 48.9 |
| 75 mg LY3031207 and Simvastatin | Pharmacokinetics: Area Under the Concentration Curve (AUC) of Simvastatin | 8.97 nanograms*hours/milliliter (hr*ng/mL) | Geometric Coefficient of Variation 70.1 |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207
Maximum concentration (Cmax) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm.
Time frame: Predose up to 48 hours post last dose at Day 28
Population: Participants who received at least one dose of LY3031207 with evaluable Cmax data at Day 28. Participants who had incomplete data due to early discontinuation were not analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 25 mg LY3031207 | Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207 | 1120 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 34.3 |
| 75 mg LY3031207 and Simvastatin | Pharmacokinetics: Maximum Concentration (Cmax) of LY3031207 | 2290 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 42.4 |
Secondary
Pharmacokinetics: Maximum Concentration (Cmax) of Simvastatin
Time frame: Predose up to 48 hours post dose at Day -3 and Day 28
Population: Participants dosed with 75 mg LY3031207 from Days 1 through 28 and with oral administration of 10 mg open-label simvastatin on Days -3 and 28 and who had complete pharmacokinetic profiles following both simvastatin dosing events. Participants who had incomplete data due to early discontinuation were not analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 25 mg LY3031207 | Pharmacokinetics: Maximum Concentration (Cmax) of Simvastatin | 1.78 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 55.3 |
| 75 mg LY3031207 and Simvastatin | Pharmacokinetics: Maximum Concentration (Cmax) of Simvastatin | 3.4 nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 69.3 |
Secondary
Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3031207
Time of maximum concentration (Tmax) of LY3031207 post-repeated once daily doses at Day 28. Day 28 results were not calculated for participants who received 225 mg LY3031207 because the study was terminated prior to participants reaching 28 days of dosing for this treatment arm.
Time frame: Predose up to 48 hours post last dose at Day 28
Population: Participants who received at least one dose of LY3031207 with evaluable Tmax data at Day 28. Participants who had incomplete data due to early discontinuation were not analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 25 mg LY3031207 | Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3031207 | 2.00 hours |
| 75 mg LY3031207 and Simvastatin | Pharmacokinetics: Time of Maximum Concentration (Tmax) of LY3031207 | 3.00 hours |
Secondary
Pharmacokinetics: Time of Maximum Concentration (Tmax) of Simvastatin
Time frame: Predose up to 48 hours post dose at Day -3 and Day 28
Population: Participants dosed with 75 mg LY3031207 from Days 1 through 28 and with oral administration of 10 mg open-label simvastatin on Days -3 and 28 and who had complete pharmacokinetic profiles following both simvastatin dosing events. Participants who had incomplete data due to early discontinuation were not analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 25 mg LY3031207 | Pharmacokinetics: Time of Maximum Concentration (Tmax) of Simvastatin | 2.00 hours |
| 75 mg LY3031207 and Simvastatin | Pharmacokinetics: Time of Maximum Concentration (Tmax) of Simvastatin | 1.15 hours |