A Study of LY2940680 in Healthy Participants

Disposition of [14C]-LY2940680 Following Oral Administration in Healthy Subjects

Status

Completed

Phases

Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01746745

Enrollment

Registered

2012-12-11

Start date

2013-01-31

Completion date

2013-03-31

Last updated

2019-07-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Volunteers

Brief summary

This is a single dose study of radiolabelled LY2940680 taken by mouth in healthy participants to study how the body absorbs and removes LY2940680 from the blood. This study is for research purposes only and is not intended to treat any medical condition.

Interventions

DRUG[^14C]-LY2940680

Administered as solution by mouth

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

OTHER

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 65 Years

Healthy volunteers

Yes

Inclusion criteria

* Generally healthy sterile males or surgically sterile females or postmenopausal females, as determined by medical history and laboratory assessments * Have a body mass index (BMI) of 18.5 to 32.0 kilograms per square meter (kg/m\^2), inclusive

Exclusion criteria

* Regularly use known drugs of abuse and/or show positive findings on urinary drug screening * Have consumed herbal supplements, grapefruit juice, grapefruits, grapefruit containing products, Seville orange juice, Seville oranges, star fruit, or star fruit juice within 7 days prior to dosing or intend to consume during the study * Have donated blood of more than 500 milliliters (mL) within the last month * Have participated in a \[\^14C\]-study within the last 6 months prior to admission for this study * Exposure to significant radiation within 12 months prior to dose (for example, serial X-ray or computed tomography scans, barium meal, current employment in a job requiring radiation exposure monitoring) * Have a pattern less than once per 2 days to expel feces from the bowel through the rectum or acute constipation within 3 weeks of the day prior to dose

Design outcomes

Primary

Measure	Time frame	Description
Fecal Excretion of LY2940680 Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered	Predose up to 14 days postdose. Samples collected at 24-h intervals.	The percentage of the total radioactive dose administered that was excreted in feces = \[(amount of radioactivity recovered in feces)/(radioactive dose administered)\]\*100.
Urinary Excretion of LY2940680 Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered	Predose up to 14 days postdose. Samples collected at 6-h intervals on Day 1 (0-6, 6-12, and 12-24 h postdose) and at 24-h intervals thereafter.	The percentage of the total radioactive dose administered that was excreted in urine=\[(amount of radioactivity recovered in urine)/(radioactive dose administered)\]\*100.

Secondary

Measure	Time frame	Description
PK of LY2940680, LSN3185556, and Radioactivity: Time of Maximum Observed Concentration (Tmax)	Predose up to 14 days postdose. Samples collected at 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 h postdose on Day 1 and every 24 h thereafter.	The Tmax of LY2940680, LSN3185556, and total radioactivity in plasma are reported, as well as the Tmax for total radioactivity in whole blood.
Plasma PK of LY2940680 and LSN3185556: Area Under the Concentration-Time Curve From Time 0 to the Last Time Point With a Measurable Concentration [AUC(0 to Tlast)]	Predose up to 14 days postdose. Samples collected at 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 h postdose on Day 1 and every 24 h thereafter.	—
PK of Radioactivity: AUC(0 to Tlast)	Predose up to 14 days postdose. Samples collected at 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 h postdose on Day 1 and every 24 h thereafter.	AUC(0 to Tlast) of total radioactivity in plasma and whole blood are reported in nanograms\hour equivalents per gram (ng\h Eq/g).
Plasma PK of LY2940680 and LSN3185556: Maximum Observed Concentration (Cmax)	Predose up to 14 days postdose. Samples collected at 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 h postdose on Day 1 and every 24 h thereafter	The Cmax of LY2940680 and its equipotent active metabolite in the free base form, LSN3185556, is reported.
Relative Abundance of LY2940680 and the Metabolites of LY2940680 in Urine	Predose up to 4 days postdose. Samples collected at 6-h intervals on Day 1 (0-6, 6-12, and 12-24 h postdose) and at 24-h intervals thereafter.	Relative abundance was expressed and calculated as the percentage of administered dose excreted in urine=\[(percentage of radioactivity in peak)/100\]\*(percentage of dose in sample). Metabolites with a relative abundance ≤1% are not reported.
Relative Abundance of LY2940680, the Metabolites of LY2940680, and LSN3185556 in Feces	Predose up to 8 days postdose. Samples collected at 24-h intervals.	Relative abundance was expressed and calculated as the percentage of the administered dose excreted in feces=\[(percentage of radioactivity in peak)/100\]\*(percentage of dose in sample). Metabolites with a relative abundance ≤1% are not reported.
Relative Abundance of LY2940680 and the Metabolites of LY2940680 in Plasma	Day 1 up to 3 days postdose. Samples collected at 2, 3, 4, 6, and 8 h postdose on Day 1 and every 24 h thereafter.	Relative abundance was expressed and calculated as the percentage of plasma sample radioactivity=\[(radioactivity in peak)/(radioactivity in sample)\]\*100. Metabolites with a relative abundance ≤6% are not reported.
PK of Radioactivity: Cmax	Predose up to 14 days postdose. Samples collected at 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 h postdose on Day 1 and every 24 h thereafter.	—

Countries

United States

Participant flow

Pre-assignment details

Participants completed study at 14 days postdose or earlier if ≥90% of administered radioactivity recovered or 24-hour (h) urine and fecal samples from 2 consecutive collections each had radioactivity levels \<1.0% of total administered radioactivity in urine and feces combined.

Participants by arm

Arm	Count
[^14C]-LY2940680 Single 100-mg LY2940680 dose containing 100 microCuries of \[\^14C\]-LY2940680, administered as an oral solution.	6
Total	6

Baseline characteristics

Characteristic	[^14C]-LY2940680
Age, Customized 44 to 59 years	6 Participants
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	1 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	5 Participants
Region of Enrollment United States	6 Participants
Sex: Female, Male Female	6 Participants
Sex: Female, Male Male	0 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	3 / 6
serious Total, serious adverse events	0 / 6

Outcome results

Primary

Fecal Excretion of LY2940680 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 feces = \[(amount of radioactivity recovered in feces)/(radioactive dose administered)\]\*100.

Time frame: Predose up to 14 days postdose. Samples collected at 24-h intervals.

Population: Enrolled participants who received study drug and had evaluable pharmacokinetic (PK) data.

Arm	Measure	Value (MEAN)	Dispersion
[^14C]-LY2940680	Fecal Excretion of LY2940680 Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered	82.7 percentage of dose administered	Standard Deviation 2.81

Primary

Urinary Excretion of LY2940680 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=\[(amount of radioactivity recovered in urine)/(radioactive dose administered)\]\*100.

Time frame: Predose up to 14 days postdose. Samples collected at 6-h intervals on Day 1 (0-6, 6-12, and 12-24 h postdose) and at 24-h intervals thereafter.