Trial Outcomes & Findings for A Study of LY2940680 in Healthy Participants (NCT NCT01746745)

NCT ID: NCT01746745

Last Updated: 2019-07-22

Results Overview

The percentage of the total radioactive dose administered that was excreted in feces = \[(amount of radioactivity recovered in feces)/(radioactive dose administered)\]\*100.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 6 participants
• Primary outcome timeframe: Predose up to 14 days postdose. Samples collected at 24-h intervals.
• Results posted on: 2019-07-22

Participant Flow

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.

Participant milestones

Measure	[^14C]-LY2940680 Single 100-milligram (mg) LY2940680 dose containing 100 microCuries of carbon-14-labeled LY2940680 (\[\^14C\]-LY2940680), administered as an oral solution.
Overall Study STARTED	6
Overall Study Received Study Drug	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of LY2940680 in Healthy Participants

Baseline characteristics by cohort

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

PRIMARY outcome

Timeframe: 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.

The percentage of the total radioactive dose administered that was excreted in feces = [(amount of radioactivity recovered in feces)/(radioactive dose administered)]*100.

Outcome measures

Measure	[^14C]-LY2940680 n=6 Participants Single 100-mg LY2940680 dose containing 100 microCuries of \[\^14C\]-LY2940680, administered as an oral solution.
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 outcome

Timeframe: 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.

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

The percentage of the total radioactive dose administered that was excreted in urine=[(amount of radioactivity recovered in urine)/(radioactive dose administered)]*100.

Outcome measures

Measure	[^14C]-LY2940680 n=6 Participants Single 100-mg LY2940680 dose containing 100 microCuries of \[\^14C\]-LY2940680, administered as an oral solution.
Urinary Excretion of LY2940680 Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered	14.6 percentage of dose administered Standard Deviation 1.68

SECONDARY outcome

Timeframe: 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

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

The Cmax of LY2940680 and its equipotent active metabolite in the free base form, LSN3185556, is reported.

Outcome measures

Measure	[^14C]-LY2940680 n=6 Participants Single 100-mg LY2940680 dose containing 100 microCuries of \[\^14C\]-LY2940680, administered as an oral solution.
Plasma PK of LY2940680 and LSN3185556: Maximum Observed Concentration (Cmax) Plasma LY2940680	831 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 6
Plasma PK of LY2940680 and LSN3185556: Maximum Observed Concentration (Cmax) Plasma LSN3185556	1210 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 25

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	[^14C]-LY2940680 n=6 Participants Single 100-mg LY2940680 dose containing 100 microCuries of \[\^14C\]-LY2940680, administered as an oral solution.
PK of Radioactivity: Cmax Plasma Total Radioactivity	2380 nanogram equivalents per gram (ng Eq/g) Geometric Coefficient of Variation 7
PK of Radioactivity: Cmax Whole Blood Total Radioactivity	1520 nanogram equivalents per gram (ng Eq/g) Geometric Coefficient of Variation 6

SECONDARY outcome

Timeframe: 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.

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

The Tmax of LY2940680, LSN3185556, and total radioactivity in plasma are reported, as well as the Tmax for total radioactivity in whole blood.

Outcome measures

Measure	[^14C]-LY2940680 n=6 Participants Single 100-mg LY2940680 dose containing 100 microCuries of \[\^14C\]-LY2940680, administered as an oral solution.
PK of LY2940680, LSN3185556, and Radioactivity: Time of Maximum Observed Concentration (Tmax) Plasma LY2940680	1.51 h Interval 1.0 to 3.0
PK of LY2940680, LSN3185556, and Radioactivity: Time of Maximum Observed Concentration (Tmax) Plasma LSN3185556	2.50 h Interval 2.0 to 4.02
PK of LY2940680, LSN3185556, and Radioactivity: Time of Maximum Observed Concentration (Tmax) Plasma Total Radioactivity	2.00 h Interval 1.0 to 3.0
PK of LY2940680, LSN3185556, and Radioactivity: Time of Maximum Observed Concentration (Tmax) Whole Blood Total Radioactivity	2.00 h Interval 1.0 to 3.0

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Measure	[^14C]-LY2940680 n=6 Participants Single 100-mg LY2940680 dose containing 100 microCuries of \[\^14C\]-LY2940680, administered as an oral solution.
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)] Plasma LY2940680	5680 nanograms*hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 19
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)] Plasma LSN3185556	20400 nanograms*hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 32

SECONDARY outcome

Timeframe: 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.

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

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

Outcome measures

Measure	[^14C]-LY2940680 n=6 Participants Single 100-mg LY2940680 dose containing 100 microCuries of \[\^14C\]-LY2940680, administered as an oral solution.
PK of Radioactivity: AUC(0 to Tlast) Plasma Total Radioactivity	64800 ng*h Eq/g Geometric Coefficient of Variation 16
PK of Radioactivity: AUC(0 to Tlast) Whole Blood Total Radioactivity	38200 ng*h Eq/g Geometric Coefficient of Variation 18

SECONDARY outcome

Timeframe: 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.

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

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.

Outcome measures

Measure	[^14C]-LY2940680 n=6 Participants Single 100-mg LY2940680 dose containing 100 microCuries of \[\^14C\]-LY2940680, administered as an oral solution.
Relative Abundance of LY2940680 and the Metabolites of LY2940680 in Plasma LY2940680 (parent)	11.1 percentage of sample radioactivity Standard Deviation 2.54
Relative Abundance of LY2940680 and the Metabolites of LY2940680 in Plasma Metabolite M75 (LSN3185556)	52.0 percentage of sample radioactivity Standard Deviation 5.14
Relative Abundance of LY2940680 and the Metabolites of LY2940680 in Plasma Metabolite M63	17.1 percentage of sample radioactivity Standard Deviation 1.71

SECONDARY outcome

Timeframe: 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.

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

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.

Outcome measures

Measure	[^14C]-LY2940680 n=6 Participants Single 100-mg LY2940680 dose containing 100 microCuries of \[\^14C\]-LY2940680, administered as an oral solution.
Relative Abundance of LY2940680 and the Metabolites of LY2940680 in Urine LY2940680 (parent)	0.105 percentage of administered dose excreted Standard Deviation 0.0937
Relative Abundance of LY2940680 and the Metabolites of LY2940680 in Urine Metabolite M43	2.87 percentage of administered dose excreted Standard Deviation 0.816
Relative Abundance of LY2940680 and the Metabolites of LY2940680 in Urine Metabolite M63	1.82 percentage of administered dose excreted Standard Deviation 0.740

SECONDARY outcome

Timeframe: Predose up to 8 days postdose. Samples collected at 24-h intervals.

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

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.

Outcome measures

Measure	[^14C]-LY2940680 n=6 Participants Single 100-mg LY2940680 dose containing 100 microCuries of \[\^14C\]-LY2940680, administered as an oral solution.
Relative Abundance of LY2940680, the Metabolites of LY2940680, and LSN3185556 in Feces LY2940680 (parent)	0.431 percentage of administered dose excreted Standard Deviation 0.313
Relative Abundance of LY2940680, the Metabolites of LY2940680, and LSN3185556 in Feces Metabolite M43	37.1 percentage of administered dose excreted Standard Deviation 1.65
Relative Abundance of LY2940680, the Metabolites of LY2940680, and LSN3185556 in Feces Metabolite M49	3.04 percentage of administered dose excreted Standard Deviation 0.861
Relative Abundance of LY2940680, the Metabolites of LY2940680, and LSN3185556 in Feces Metabolite M73	3.19 percentage of administered dose excreted Standard Deviation 1.43
Relative Abundance of LY2940680, the Metabolites of LY2940680, and LSN3185556 in Feces LSN3185556	2.90 percentage of administered dose excreted Standard Deviation 1.09

Adverse Events

[^14C]-LY2940680

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	[^14C]-LY2940680 n=6 participants at risk Single 100-mg LY2940680 dose containing 100 microCuries of \[\^14C\]-LY2940680, administered as an oral solution.
Gastrointestinal disorders Abdominal distension	16.7% 1/6 • Number of events 1
Gastrointestinal disorders Diarrhoea	33.3% 2/6 • Number of events 2
Musculoskeletal and connective tissue disorders Soft tissue mass	16.7% 1/6 • Number of events 1
Nervous system disorders Headache	16.7% 1/6 • Number of events 1

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: GT60