Healthy
Conditions
Brief summary
The purpose of this study is to measure how much LY3337641 gets into the bloodstream and how long it takes the body to get rid of it. In addition, the safety and tolerability of the study drug will be evaluated. Participants will be admitted to a clinical research unit (CRU) the day before dosing. Participants remain confined to the CRU for at least 7 days. Participants may be discharged from the CRU any time after 7 days post-dose (Day 8), and up to a maximum of 21 days post-dose (Day 22). This study will last approximately 30 days for each participant, not including screening. Screening is required within 28 days prior to the start of the study.
Interventions
DRUG[¹⁴C]-LY3337641
Administered orally
Sponsors
Eli Lilly and Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Overtly healthy males, as determined by medical history and physical examination * Have a body mass index (BMI) between 18.5 and 32.0 kilograms per meter squared (kg/m²) * Have clinical laboratory test results within normal reference range for the population or investigative site, or results with acceptable deviations that are judged to be not clinically significant by the investigator * Have venous access sufficient to allow for blood sampling as per the protocol * Are able and willing to give signed informed consent * Generally have a minimum of 1 bowel movement per day
Exclusion criteria
* Have participated, within the last 30 days, in a clinical trial involving an investigational product. If the previous investigational product has a long half-life, 3 months or 5 half-lives (whichever is longer, if known) should have passed * Have a significant history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI) (cholecystectomy not acceptable), endocrine, hematological, dermatologic, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the investigational product; or of interfering with the interpretation of data * Regularly use known drugs of abuse and/or show positive findings on urinary drug screening * Have used or intend to use over-the-counter or prescription medication, including herbal medications, within 14 days prior to dosing * Have donated blood of more than 500 milliliter (mL) within the month prior to screening * Have an average weekly alcohol intake that exceeds 21 units per week, and are unwilling to stop alcohol consumption for 48 hours prior to admission, and while resident in the clinical research unit (CRU) * In the opinion of the investigator or sponsor, are unsuitable for inclusion in the study * Have had exposure to significant diagnostic, therapeutic, or employment related radiation within 12 months prior to dosing (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 (per 21 CFR 361.1): less than 5000 Milli-rem (mrem) /year whole body annual exposure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Urinary Excretion of Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered | Baseline up to 22 days | Urinary excretion samples from each participant were measured by liquid scintillation counting. The radioactive counts detected in urine samples were each divided by the theoretical radioactive count in the total radioactive dose administered and multiplied by 100% to arrive at a percentage of total radioactive dose excreted in urine and feces. |
| Fecal Excretion of Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered | Baseline up to 22 days | Fecal excretion samples from each participant were measured by liquid scintillation counting. The radioactive counts detected in fecal samples were each divided by the theoretical radioactive count in the total radioactive dose administered and multiplied by 100% to arrive at a percentage of total radioactive dose excreted in feces. |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetics: Maximum Observed Concentration (Cmax) of Whole Blood Radioactivity | Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264 and 312 hours post dose |
| Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC 0 to ∞) of Plasma LY3337641 | Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264 and 312 hours post dose |
| Pharmacokinetics: Maximum Observed Concentration (Cmax) of Plasma LY3337641 | Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264 and 312 hours post dose |
| Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC 0 to ∞) of Whole Blood Radioactivity | Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264 and 312 hours post dose |
| Pharmacokinetics: Total Number of Measurable Metabolites of LY3337641 in Plasma, Urine and Feces | Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264, and 312 hours postdose |
| Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC 0 to ∞) of Plasma Radioactivity | Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264 and 312 hours post dose |
| Pharmacokinetics: Maximum Observed Concentration (Cmax) of Plasma Radioactivity | Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264 and 312 hours post dose |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 20mg [¹⁴C]-LY3337641 Participants received 20 mg oral dose of LY3337641 containing 120 microcuries of radioactivity. | 6 |
| Total | 6 |
Baseline characteristics
| Characteristic | 20mg [¹⁴C]-LY3337641 |
|---|---|
| Age, Continuous | 34.3 Years STANDARD_DEVIATION 11.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 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 | 1 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 | 5 Participants |
| Region of Enrollment United States | 6 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 1 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
Primary
Fecal Excretion of Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered
Fecal excretion samples from each participant were measured by liquid scintillation counting. The radioactive counts detected in fecal samples were each divided by the theoretical radioactive count in the total radioactive dose administered and multiplied by 100% to arrive at a percentage of total radioactive dose excreted in feces.
Time frame: Baseline up to 22 days
Population: All participants who received the study drug and have evaluable PK data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 20 mg [¹⁴C]-LY3337641 | Fecal Excretion of Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered | 86.4 Percentage of total dose | Standard Deviation 5.1 |
Primary
Urinary Excretion of Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered
Urinary excretion samples from each participant were measured by liquid scintillation counting. The radioactive counts detected in urine samples were each divided by the theoretical radioactive count in the total radioactive dose administered and multiplied by 100% to arrive at a percentage of total radioactive dose excreted in urine and feces.
Time frame: Baseline up to 22 days
Population: All participants who received the study drug and have evaluable pharmacokinetic (PK) data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 20 mg [¹⁴C]-LY3337641 | Urinary Excretion of Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered | 2.9 Percentage of total dose | Standard Deviation 1 |
Secondary
Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC 0 to ∞) of Plasma LY3337641
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264 and 312 hours post dose
Population: All participants who received the study drug and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg [¹⁴C]-LY3337641 | Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC 0 to ∞) of Plasma LY3337641 | 370 Nanograms*hours per milliliter (ng*h/mL) | Geometric Coefficient of Variation 25 |
Secondary
Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC 0 to ∞) of Plasma Radioactivity
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264 and 312 hours post dose
Population: All participants who received the study drug and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg [¹⁴C]-LY3337641 | Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC 0 to ∞) of Plasma Radioactivity | 1240 ng-equivalents*h/gram (ng-equiv*h/g) | Geometric Coefficient of Variation 51 |
Secondary
Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC 0 to ∞) of Whole Blood Radioactivity
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264 and 312 hours post dose
Population: All participants who received the study drug and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg [¹⁴C]-LY3337641 | Pharmacokinetics: Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC 0 to ∞) of Whole Blood Radioactivity | 5840 ng*h/mL | Geometric Coefficient of Variation 105 |
Secondary
Pharmacokinetics: Maximum Observed Concentration (Cmax) of Plasma LY3337641
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264 and 312 hours post dose
Population: All participants who received the study drug and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg [¹⁴C]-LY3337641 | Pharmacokinetics: Maximum Observed Concentration (Cmax) of Plasma LY3337641 | 77.9 Nanograms/milliliter (ng/mL) | Geometric Coefficient of Variation 26 |
Secondary
Pharmacokinetics: Maximum Observed Concentration (Cmax) of Plasma Radioactivity
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264 and 312 hours post dose
Population: All participants who received the study drug and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg [¹⁴C]-LY3337641 | Pharmacokinetics: Maximum Observed Concentration (Cmax) of Plasma Radioactivity | 122 nanogram equivalents/g (ng-equiv/g) | Geometric Coefficient of Variation 25 |
Secondary
Pharmacokinetics: Maximum Observed Concentration (Cmax) of Whole Blood Radioactivity
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264 and 312 hours post dose
Population: All participants who received the study drug and have evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 20 mg [¹⁴C]-LY3337641 | Pharmacokinetics: Maximum Observed Concentration (Cmax) of Whole Blood Radioactivity | 67.5 ng/mL | Geometric Coefficient of Variation 24 |
Secondary
Pharmacokinetics: Total Number of Measurable Metabolites of LY3337641 in Plasma, Urine and Feces
Time frame: Predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264, and 312 hours postdose
Population: All participants who received the study drug and have evaluable PK data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 20 mg [¹⁴C]-LY3337641 | Pharmacokinetics: Total Number of Measurable Metabolites of LY3337641 in Plasma, Urine and Feces | Plasma | 6 Number of Metabolites |
| 20 mg [¹⁴C]-LY3337641 | Pharmacokinetics: Total Number of Measurable Metabolites of LY3337641 in Plasma, Urine and Feces | Urine | 4 Number of Metabolites |
| 20 mg [¹⁴C]-LY3337641 | Pharmacokinetics: Total Number of Measurable Metabolites of LY3337641 in Plasma, Urine and Feces | Feces | 8 Number of Metabolites |