A Study of LY2940680 in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01746745
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 1.9
• Patients Per Site Per Month: 3.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: [^14C]-LY2940680	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Disposition of [14C]-LY2940680 Following Oral Administration in Healthy Subjects
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Mar 1, 2013
• Actual Study Completion Date: Mar 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: [^14C]-LY2940680 Single 100 milligram (mg) dose of LY2940680 containing 100 microCuries of carbon-14-labeled LY2940680 ([^14C]-LY2940680)	Drug: [^14C]-LY2940680; Administered as solution by mouth

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. 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.]

3. 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.

4. 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.]

5. 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).

6. 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.

7. 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.

8. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Madison	Wisconsin	United States	53704

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01746745
• Other Study ID Numbers: 14892; I4J-MC-HHBF
• First Posted: Dec 11, 2012
• Last Update Posted: Jul 22, 2019
• Last Verified: May 1, 2019

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	[^14C]-LY2940680
Arm/Group Description	Single 100-milligram (mg) LY2940680 dose containing 100 microCuries of carbon-14-labeled LY2940680 ([^14C]-LY2940680), administered as an oral solution.
Period Title: Overall Study
STARTED	6
Received Study Drug	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	[^14C]-LY2940680
Arm/Group Description	Single 100-mg LY2940680 dose containing 100 microCuries of [^14C]-LY2940680, administered as an oral solution.
Overall Participants	6
Age, Customized (Count of Participants)
44 to 59 years	6 100%
Sex: Female, Male (Count of Participants)
Female	6 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	6 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 16.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	5 83.3%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Fecal Excretion of LY2940680 Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	[^14C]-LY2940680
Arm/Group Description	Single 100-mg LY2940680 dose containing 100 microCuries of [^14C]-LY2940680, administered as an oral solution.
Measure Participants	6
Mean (Standard Deviation) [percentage of dose administered]	82.7 (2.81)

2. Primary Outcome

Title	Urinary Excretion of LY2940680 Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered
Description	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.

Outcome Measure Data

Analysis Population Description

Enrolled participants who received study drug and had evaluable PK data.

Arm/Group Title	[^14C]-LY2940680
Arm/Group Description	Single 100-mg LY2940680 dose containing 100 microCuries of [^14C]-LY2940680, administered as an oral solution.
Measure Participants	6
Mean (Standard Deviation) [percentage of dose administered]	14.6 (1.68)

3. Secondary Outcome

Title	Plasma PK of LY2940680 and LSN3185556: Maximum Observed Concentration (Cmax)
Description	The Cmax of LY2940680 and its equipotent active metabolite in the free base form, LSN3185556, is reported.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Enrolled participants who received study drug and had evaluable PK data.

Arm/Group Title	[^14C]-LY2940680
Arm/Group Description	Single 100-mg LY2940680 dose containing 100 microCuries of [^14C]-LY2940680, administered as an oral solution.
Measure Participants	6
Plasma LY2940680	831 (6)
Plasma LSN3185556	1210 (25)

4. Secondary Outcome

Title	PK of Radioactivity: Cmax
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Enrolled participants who received study drug and had evaluable PK data.

Arm/Group Title	[^14C]-LY2940680
Arm/Group Description	Single 100-mg LY2940680 dose containing 100 microCuries of [^14C]-LY2940680, administered as an oral solution.
Measure Participants	6
Plasma Total Radioactivity	2380 (7)
Whole Blood Total Radioactivity	1520 (6)

5. Secondary Outcome

Title	PK of LY2940680, LSN3185556, and Radioactivity: Time of Maximum Observed Concentration (Tmax)
Description	The Tmax of LY2940680, LSN3185556, and total radioactivity in plasma are reported, as well as the Tmax for total radioactivity in whole blood.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Enrolled participants who received study drug and had evaluable PK data.

Arm/Group Title	[^14C]-LY2940680
Arm/Group Description	Single 100-mg LY2940680 dose containing 100 microCuries of [^14C]-LY2940680, administered as an oral solution.
Measure Participants	6
Plasma LY2940680	1.51
Plasma LSN3185556	2.50
Plasma Total Radioactivity	2.00
Whole Blood Total Radioactivity	2.00

6. Secondary Outcome

Title	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)]
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Enrolled participants who received study drug and had evaluable PK data.

Arm/Group Title	[^14C]-LY2940680
Arm/Group Description	Single 100-mg LY2940680 dose containing 100 microCuries of [^14C]-LY2940680, administered as an oral solution.
Measure Participants	6
Plasma LY2940680	5680 (19)
Plasma LSN3185556	20400 (32)

7. Secondary Outcome

Title	PK of Radioactivity: AUC(0 to Tlast)
Description	AUC(0 to Tlast) of total radioactivity in plasma and whole blood are reported in nanograms*hour equivalents per gram (ng*h Eq/g).
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Enrolled participants who received study drug and had evaluable PK data.

Arm/Group Title	[^14C]-LY2940680
Arm/Group Description	Single 100-mg LY2940680 dose containing 100 microCuries of [^14C]-LY2940680, administered as an oral solution.
Measure Participants	6
Plasma Total Radioactivity	64800 (16)
Whole Blood Total Radioactivity	38200 (18)

8. Secondary Outcome

Title	Relative Abundance of LY2940680 and the Metabolites of LY2940680 in Plasma
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Enrolled participants who received study drug and had evaluable PK data.

Arm/Group Title	[^14C]-LY2940680
Arm/Group Description	Single 100-mg LY2940680 dose containing 100 microCuries of [^14C]-LY2940680, administered as an oral solution.
Measure Participants	6
LY2940680 (parent)	11.1 (2.54)
Metabolite M75 (LSN3185556)	52.0 (5.14)
Metabolite M63	17.1 (1.71)

9. Secondary Outcome

Title	Relative Abundance of LY2940680 and the Metabolites of LY2940680 in Urine
Description	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.
Time Frame	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.

Outcome Measure Data

Analysis Population Description

Enrolled participants who received study drug and had evaluable PK data.

Arm/Group Title	[^14C]-LY2940680
Arm/Group Description	Single 100-mg LY2940680 dose containing 100 microCuries of [^14C]-LY2940680, administered as an oral solution.
Measure Participants	6
LY2940680 (parent)	0.105 (0.0937)
Metabolite M43	2.87 (0.816)
Metabolite M63	1.82 (0.740)

10. Secondary Outcome

Title	Relative Abundance of LY2940680, the Metabolites of LY2940680, and LSN3185556 in Feces
Description	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.
Time Frame	Predose up to 8 days postdose. Samples collected at 24-h intervals.

Outcome Measure Data

Analysis Population Description

Enrolled participants who received study drug and had evaluable PK data.

Arm/Group Title	[^14C]-LY2940680
Arm/Group Description	Single 100-mg LY2940680 dose containing 100 microCuries of [^14C]-LY2940680, administered as an oral solution.
Measure Participants	6
LY2940680 (parent)	0.431 (0.313)
Metabolite M43	37.1 (1.65)
Metabolite M49	3.04 (0.861)
Metabolite M73	3.19 (1.43)
LSN3185556	2.90 (1.09)

Adverse Events

Arm/Group Title	[^14C]-LY2940680
Arm/Group Description	Single 100-mg LY2940680 dose containing 100 microCuries of [^14C]-LY2940680, administered as an oral solution.
All Cause Mortality
	[^14C]-LY2940680
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	[^14C]-LY2940680
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	[^14C]-LY2940680
	Affected / at Risk (%)	# Events
Total	3/6 (50%)
Gastrointestinal disorders
Abdominal distension	1/6 (16.7%)	1
Diarrhoea	2/6 (33.3%)	2
Musculoskeletal and connective tissue disorders
Soft tissue mass	1/6 (16.7%)	1
Nervous system disorders
Headache	1/6 (16.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.