Healthy
Conditions
Brief summary
This type of study is called a radiolabeled study. For this study, LY3039478 (study drug) has been specially prepared to contain radiolabeled carbon \[¹⁴C\]. \[¹⁴C\] is a naturally occurring radioactive form of the element carbon. This study will help determine how the drug appears in the blood, urine, and stool after it is administered by mouth to healthy people. Information about any side effects that may occur will also be collected. This study will last about 10 weeks for each participant.
Interventions
DRUGLY3039478
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
\- Have a body mass index (BMI) of 18 to 32 kilogram per meter square (kg/m²), inclusive
Exclusion criteria
* Have previously completed or withdrawn from this study or any other study investigating LY3039478, and have previously received the investigational product * Have known allergies to LY3039478, related compounds or any components of the formulation, or history of significant atopy * Have had exposure to significant diagnostic, therapeutic, or employment-related radiation within 12 months prior to dosing (eg, serial x-ray or computed tomography scans, barium meal, current employment in a job requiring radiation exposure monitoring) * Have participated in a \[¹⁴C\] study within the last 6 months prior to admission for this study. The total 12-month exposure from this study and a maximum of one other previous \[¹⁴C\]-study within 6 to 12 months of this study must be within the Code of Federal Regulations (CFR) recommended levels considered safe: less than 5000 millirem (mrem)/year whole body annual exposure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary and Fecal Excretion of Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered | Predose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, and 312 hours postdose | To determine the disposition of radioactivity and LY3039478 in healthy participants following oral administration of a single dose 14C-labeled LY3039478. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3039478 | Predose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | The AUC\[0-inf\]) for plasma LY3039478 was evaluated by using a combination of the linear and logarithmic trapezoidal methods (linear-log trapezoidal rule). |
| Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of Total Plasma Radioactivity | Predose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | The AUC\[0-inf\]) for total plasma radioactivity was evaluated by using a combination of the linear and logarithmic trapezoidal methods (linear-log trapezoidal rule). |
| Pharmacokinetics: Maximum Observed Concentration (Cmax) of LY3039478 | Predose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | The Cmax of LY3039478 was evaluated. |
| Pharmacokinetics: Maximum Observed Concentration (Cmax) of Total Plasma Radioactivity | Predose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose | Cmax of total plasma radioactivity was evaluated. |
| Total Number of Metabolites of LY3039478 in Plasma, Urine and Feces | Predose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose. | Following oral administration, radio high performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) profiles were obtained from analysis of plasma, urine and feces. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 75 mg [14C2] LY3039478 Participants received approximately 75 mg \[14C2\] LY3039478 containing approximately 100 μCi \[14C2\] LY3039478. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | 75 mg [14C2] LY3039478 |
|---|---|
| Age, Continuous | 55.0 years STANDARD_DEVIATION 8.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 6 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Urinary and Fecal Excretion of Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered
To determine the disposition of radioactivity and LY3039478 in healthy participants following oral administration of a single dose 14C-labeled LY3039478.
Time frame: Predose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, and 312 hours postdose
Population: All participants who received the \[14C2\]-LY3039478 dose.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 75 mg [14C2] LY3039478 | Urinary and Fecal Excretion of Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered | 90.2 percentage of administered radioactivity | Standard Deviation 2.32 |
Secondary
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3039478
The AUC\[0-inf\]) for plasma LY3039478 was evaluated by using a combination of the linear and logarithmic trapezoidal methods (linear-log trapezoidal rule).
Time frame: Predose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All the participants who received \[14C2\]-LY3039478 dose and had evaluable data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 75 mg [14C2] LY3039478 | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of LY3039478 | 2570 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 11 |
Secondary
Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of Total Plasma Radioactivity
The AUC\[0-inf\]) for total plasma radioactivity was evaluated by using a combination of the linear and logarithmic trapezoidal methods (linear-log trapezoidal rule).
Time frame: Predose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All the participants who received \[14C2\]-LY3039478 dose and had evaluable data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 75 mg [14C2] LY3039478 | Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of Total Plasma Radioactivity | 26100 ng quivalents*hour/gram (ng equiv.h/g) | Geometric Coefficient of Variation 21 |
Secondary
Pharmacokinetics: Maximum Observed Concentration (Cmax) of LY3039478
The Cmax of LY3039478 was evaluated.
Time frame: Predose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All the participants who received \[14C2\]-LY3039478 dose and had evaluable data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 75 mg [14C2] LY3039478 | Pharmacokinetics: Maximum Observed Concentration (Cmax) of LY3039478 | 517 Nanograms/milliliter (ng/ml) | Geometric Coefficient of Variation 15 |
Secondary
Pharmacokinetics: Maximum Observed Concentration (Cmax) of Total Plasma Radioactivity
Cmax of total plasma radioactivity was evaluated.
Time frame: Predose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose
Population: All participants who received \[14C2\]-LY3039478 dose and had evaluable data for this outcome.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 75 mg [14C2] LY3039478 | Pharmacokinetics: Maximum Observed Concentration (Cmax) of Total Plasma Radioactivity | 1060 Nanograms equivalents/gram (ng equiv/g) | Geometric Coefficient of Variation 10 |
Secondary
Total Number of Metabolites of LY3039478 in Plasma, Urine and Feces
Following oral administration, radio high performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) profiles were obtained from analysis of plasma, urine and feces.
Time frame: Predose, and at 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, and 168 hours postdose.
Population: All participants who received \[14C2\]-LY3039478 dose. For the feces profiling, only one participant had quantifiable radioactive dose recovered in feces adequate for metabolite profiling and was therefore eligible for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 75 mg [14C2] LY3039478 | Total Number of Metabolites of LY3039478 in Plasma, Urine and Feces | Number of Metabolites of LY3039478 in Plasma | 8 Metabolites |
| 75 mg [14C2] LY3039478 | Total Number of Metabolites of LY3039478 in Plasma, Urine and Feces | Number of Metabolites of LY3039478 in Urine | 10 Metabolites |
| 75 mg [14C2] LY3039478 | Total Number of Metabolites of LY3039478 in Plasma, Urine and Feces | Number of Metabolites of LY3039478 in Feces | 3 Metabolites |