Healthy Volunteers
Conditions
Brief summary
This type of study is called a radiolabeled study. For this study, LY2835219 (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 understand how the drug appears in the blood, urine, and stool after it is administered. In addition, this study will also evaluate the safety and tolerability of a single dose of LY2835219 when given to healthy participants. Information about any side effects that may occur will also be collected. This study will last about 3 weeks for each participant, not including screening.
Interventions
DRUG[^14C]-LY2835219
Administered as oral solution
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
* Overtly healthy male or female participants as determined by medical history and physical examination * Male participants will be sterile * Female participants will be surgically sterile or postmenopausal * Have a body mass index (BMI) of 18 to 29 kilograms per square meter (kg/m\^2) * Have venous access sufficient to allow for blood sampling
Exclusion criteria
* Have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, 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 * Gastrointestinal disorders causing clinically significant symptoms such as nausea, vomiting, and diarrhea, or malabsorption syndromes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary and Fecal Excretion of LY2835219-Related Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered | Predose up to Day 14 postdose; Fecal samples collected at 24-hour (h) intervals; Urine collected at 0 to 6 h, 6 to 12 h, and 12 to 24 h postdose and at 24-h intervals thereafter up to Day 14 postdose | The percentage of the total radioactive dose administered that was excreted in urine or feces = (amount of radioactive dose recovered in urine or feces / total radioactive dose administered) \* 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma PK of Radioactivity: Cmax | Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose | — |
| Plasma PK of LY2835219, Metabolite of LY2835219, and Radioactivity: Time of Maximum Observed Concentration (Tmax) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose | — |
| Plasma PK of LY2835219 and Metabolite of LY2835219: Area Under the Concentration-Time Curve From Time Zero to the Last Time Point With a Measurable Concentration [AUC(0-tlast)] | Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose | — |
| Plasma PK of Radioactivity: AUC(0 to Tlast) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose | The PK of radioactivity was measured as nanogram equivalents times hours per gram (ng Eq\*h/g). |
| Plasma Pharmacokinetics (PK) of LY2835219 and Metabolite of LY2835219: Maximum Observed Concentration (Cmax) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose | — |
| Plasma PK of Radioactivity: AUC(0-∞) | Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose | — |
| Relative Abundance of LY2835219 and Metabolites of LY2835219 Eliminated in Urine and Feces | Predose through 216 h postdose; Fecal samples collected at 24-h intervals | The abundance (as percentage dose) of LY2835219 or its metabolites eliminated in feces is calculated as = (amount of LY2835219 or its metabolites recovered in feces / total amount administered) \* 100. Due to low radioactivity of dose recovered in urine, further quantitative profiling of urine was not conducted. |
| Relative Abundance of LY2835219 and Metabolites of LY2835219 in Plasma | Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose | The relative abundance of LY2835219 or its metabolites in plasma were estimated based on AUC(0-∞) and reported as a percentage of total plasma radioactivity. The relative abundance of LY2835219 or its metabolites calculated as = \[AUC (0-∞) of LY2835219 or its metabolites in plasma / AUC (0-∞) of total plasma radioactivity\] \* 100. |
| Plasma PK of LY2835219 and Metabolite of LY2835219: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] | Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| [^14C]-LY2835219 Single 150-mg LY2835219 dose containing 5 µCi of \[\^14C\]-LY2835219, administered as an oral solution. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | [^14C]-LY2835219 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 6 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 | 4 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Urinary and Fecal Excretion of LY2835219-Related Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered
The percentage of the total radioactive dose administered that was excreted in urine or feces = (amount of radioactive dose recovered in urine or feces / total radioactive dose administered) \* 100.
Time frame: Predose up to Day 14 postdose; Fecal samples collected at 24-hour (h) intervals; Urine collected at 0 to 6 h, 6 to 12 h, and 12 to 24 h postdose and at 24-h intervals thereafter up to Day 14 postdose
Population: Participants who received study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| [^14C]-LY2835219 | Urinary and Fecal Excretion of LY2835219-Related Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered | Urine | 3.43 percentage radioactive dose administered | Standard Deviation 2.2 |
| [^14C]-LY2835219 | Urinary and Fecal Excretion of LY2835219-Related Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered | Feces | 81.0 percentage radioactive dose administered | Standard Deviation 6.71 |
Secondary
Plasma Pharmacokinetics (PK) of LY2835219 and Metabolite of LY2835219: Maximum Observed Concentration (Cmax)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose
Population: Participants who received study drug and had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| [^14C]-LY2835219 | Plasma Pharmacokinetics (PK) of LY2835219 and Metabolite of LY2835219: Maximum Observed Concentration (Cmax) | LY2835219 | 63.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 49 |
| [^14C]-LY2835219 | Plasma Pharmacokinetics (PK) of LY2835219 and Metabolite of LY2835219: Maximum Observed Concentration (Cmax) | M20 | 30.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 19 |
Secondary
Plasma PK of LY2835219 and Metabolite of LY2835219: Area Under the Concentration-Time Curve From Time Zero to the Last Time Point With a Measurable Concentration [AUC(0-tlast)]
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose
Population: Participants who received study drug and had evaluable PK AUC(0-tlast) data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| [^14C]-LY2835219 | Plasma PK of LY2835219 and Metabolite of LY2835219: Area Under the Concentration-Time Curve From Time Zero to the Last Time Point With a Measurable Concentration [AUC(0-tlast)] | LY2835219 | 2310 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 85 |
| [^14C]-LY2835219 | Plasma PK of LY2835219 and Metabolite of LY2835219: Area Under the Concentration-Time Curve From Time Zero to the Last Time Point With a Measurable Concentration [AUC(0-tlast)] | M20 | 1760 nanograms*hour/milliliter (ng*h/mL) | Geometric Coefficient of Variation 43 |
Secondary
Plasma PK of LY2835219 and Metabolite of LY2835219: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)]
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose
Population: Participants who received study drug and had evaluable PK AUC(0-∞) data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| [^14C]-LY2835219 | Plasma PK of LY2835219 and Metabolite of LY2835219: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] | LY2835219 | 2370 ng*h/mL | Geometric Coefficient of Variation 83 |
| [^14C]-LY2835219 | Plasma PK of LY2835219 and Metabolite of LY2835219: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] | M20 | 1830 ng*h/mL | Geometric Coefficient of Variation 42 |
Secondary
Plasma PK of LY2835219, Metabolite of LY2835219, and Radioactivity: Time of Maximum Observed Concentration (Tmax)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose
Population: Participants who received study drug and evaluable PK tmax data.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| [^14C]-LY2835219 | Plasma PK of LY2835219, Metabolite of LY2835219, and Radioactivity: Time of Maximum Observed Concentration (Tmax) | LY2835219 | 8.00 h |
| [^14C]-LY2835219 | Plasma PK of LY2835219, Metabolite of LY2835219, and Radioactivity: Time of Maximum Observed Concentration (Tmax) | M20 | 8.00 h |
| [^14C]-LY2835219 | Plasma PK of LY2835219, Metabolite of LY2835219, and Radioactivity: Time of Maximum Observed Concentration (Tmax) | Total Radioactivity | 8.00 h |
Secondary
Plasma PK of Radioactivity: AUC(0-∞)
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose
Population: Participants who received study drug and had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| [^14C]-LY2835219 | Plasma PK of Radioactivity: AUC(0-∞) | 7010 ng Eq*h/g | Geometric Coefficient of Variation 42 |
Secondary
Plasma PK of Radioactivity: AUC(0 to Tlast)
The PK of radioactivity was measured as nanogram equivalents times hours per gram (ng Eq\*h/g).
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose
Population: Participants who received study drug and had evaluable PK AUC(0-tlast) data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| [^14C]-LY2835219 | Plasma PK of Radioactivity: AUC(0 to Tlast) | 6580 ng Eq*h/g | Geometric Coefficient of Variation 41 |
Secondary
Plasma PK of Radioactivity: Cmax
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose
Population: Participants who received study drug and had evaluable PK Cmax data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| [^14C]-LY2835219 | Plasma PK of Radioactivity: Cmax | 123 nanogram equivalents per gram (ng Eq/g) | Geometric Coefficient of Variation 27 |
Secondary
Relative Abundance of LY2835219 and Metabolites of LY2835219 Eliminated in Urine and Feces
The abundance (as percentage dose) of LY2835219 or its metabolites eliminated in feces is calculated as = (amount of LY2835219 or its metabolites recovered in feces / total amount administered) \* 100. Due to low radioactivity of dose recovered in urine, further quantitative profiling of urine was not conducted.
Time frame: Predose through 216 h postdose; Fecal samples collected at 24-h intervals
Population: Participants who received study drug and had evaluable PK data. No participants were analyzed for relative abundance of LY2835219 and metabolites of LY2835219 in urine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| [^14C]-LY2835219 | Relative Abundance of LY2835219 and Metabolites of LY2835219 Eliminated in Urine and Feces | LY2835219 | 7 percentage of radioactive dose excreted |
| [^14C]-LY2835219 | Relative Abundance of LY2835219 and Metabolites of LY2835219 Eliminated in Urine and Feces | Metabolites | 52 percentage of radioactive dose excreted |
Secondary
Relative Abundance of LY2835219 and Metabolites of LY2835219 in Plasma
The relative abundance of LY2835219 or its metabolites in plasma were estimated based on AUC(0-∞) and reported as a percentage of total plasma radioactivity. The relative abundance of LY2835219 or its metabolites calculated as = \[AUC (0-∞) of LY2835219 or its metabolites in plasma / AUC (0-∞) of total plasma radioactivity\] \* 100.
Time frame: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose
Population: Participants who received study drug and had evaluable PK AUC(0-∞) data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| [^14C]-LY2835219 | Relative Abundance of LY2835219 and Metabolites of LY2835219 in Plasma | LY2835219 | 34 percentage of total plasma radioactivity |
| [^14C]-LY2835219 | Relative Abundance of LY2835219 and Metabolites of LY2835219 in Plasma | Metabolites | 44 percentage of total plasma radioactivity |