Trial Outcomes & Findings for Disposition of Carbon-14-Labeled LY2886721 ([^14C]-LY2886721) Following Oral Administration in Healthy Human Participants (NCT NCT01367262)

NCT ID: NCT01367262

Last Updated: 2019-09-13

Results Overview

Urinary and fecal excretion of LY2886721 radioactivity over time was expressed as a percentage of the total radioactive dose administered. The amount of drug-related material excreted in urine and feces (Ae) at a specific collection interval (i) was calculated as the product of radioactivity concentration and volume or weight. The Ae values for each collection interval were then summed and calculated as Total Ae=Ae(i1)+Ae(i2)+Ae(in). The percentage of the total radiolabeled dose administered that was excreted in feces or urine=\[(Total Ae)/(Total radioactive dose administered)\]\*100.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 6 participants
• Primary outcome timeframe: Predose up to 7 days (168 hours) postdose
• Results posted on: 2019-09-13

Participant Flow

Participants were considered to have completed the study at 9 days postdose or earlier if ≥90% of administered radioactivity recovered or 24-hour 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]-LY2886721 Single 25-milligram (mg) LY2886721 dose containing approximately 80 microCuries (μCi) of carbon-14-labeled LY2886721 (\[\^14C\]-LY2886721), administered as an oral solution.
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Disposition of Carbon-14-Labeled LY2886721 ([^14C]-LY2886721) Following Oral Administration in Healthy Human Participants

Baseline characteristics by cohort

Measure	[^14C]-LY2886721 n=6 Participants Single 25-mg LY2886721 dose containing approximately 80 μCi of \[\^14C\]-LY2886721, administered as an oral solution.
Age, Continuous	31.2 years STANDARD_DEVIATION 12.4 • n=5 Participants
Sex/Gender, Customized Males	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 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	0 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	1 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 7 days (168 hours) postdose

Population: All enrolled participants.

Urinary and fecal excretion of LY2886721 radioactivity over time was expressed as a percentage of the total radioactive dose administered. The amount of drug-related material excreted in urine and feces (Ae) at a specific collection interval (i) was calculated as the product of radioactivity concentration and volume or weight. The Ae values for each collection interval were then summed and calculated as Total Ae=Ae(i1)+Ae(i2)+Ae(in). The percentage of the total radiolabeled dose administered that was excreted in feces or urine=[(Total Ae)/(Total radioactive dose administered)]*100.

Outcome measures

Measure	[^14C]-LY2886721 n=6 Participants Single 25-mg LY2886721 dose containing approximately 80 μCi of \[\^14C\]-LY2886721, administered as an oral solution.
Percentage of Urinary and Fecal Excretion of LY2886721 Radioactivity Over Time Urine	85.7 percentage of radioactive dose Standard Deviation 2.44
Percentage of Urinary and Fecal Excretion of LY2886721 Radioactivity Over Time Feces	8.86 percentage of radioactive dose Standard Deviation 0.868

SECONDARY outcome

Timeframe: Predose up to 4 days (96 hours) postdose

Population: All enrolled participants.

Outcome measures

Measure	[^14C]-LY2886721 n=6 Participants Single 25-mg LY2886721 dose containing approximately 80 μCi of \[\^14C\]-LY2886721, administered as an oral solution.
Plasma Pharmacokinetics (PK) of LY2886721: Area Under the Concentration-Time Curve From Time 0 to Infinity [AUC(0 to Inf)]	681 hours*nanograms per milliliter (h*ng/mL) Geometric Coefficient of Variation 13

SECONDARY outcome

Timeframe: Predose up to 4 days (96 hours) postdose

Population: All enrolled participants.

AUC(0 to inf) for plasma and whole blood total radioactivity is reported as hours*nanogram equivalents per milliliter (h*ng Eq/mL).

Outcome measures

Measure	[^14C]-LY2886721 n=6 Participants Single 25-mg LY2886721 dose containing approximately 80 μCi of \[\^14C\]-LY2886721, administered as an oral solution.
PK of Radioactivity: AUC(0 to Inf) Plasma Total Radioactivity	3310 h*ng Eq/mL Geometric Coefficient of Variation 13
PK of Radioactivity: AUC(0 to Inf) Whole Blood Total Radioactivity	2470 h*ng Eq/mL Geometric Coefficient of Variation 13

SECONDARY outcome

Timeframe: Predose up to 4 days (96 hours) postdose

Population: All enrolled participants.

Outcome measures

Measure	[^14C]-LY2886721 n=6 Participants Single 25-mg LY2886721 dose containing approximately 80 μCi of \[\^14C\]-LY2886721, administered as an oral solution.
Plasma PK of LY2886721: Maximum Observed Concentration (Cmax)	56.3 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 15

SECONDARY outcome

Timeframe: Predose up to 4 days (96 hours) postdose

Population: All enrolled participants.

The Cmax of total radioactivity in plasma and whole blood are reported as nanogram equivalents per milliliter (ng Eq/mL).

Outcome measures

Measure	[^14C]-LY2886721 n=6 Participants Single 25-mg LY2886721 dose containing approximately 80 μCi of \[\^14C\]-LY2886721, administered as an oral solution.
PK of Radioactivity: Cmax Plasma Total Radioactivity	218 ng Eq/mL Geometric Coefficient of Variation 15
PK of Radioactivity: Cmax Whole Blood Total Radioactivity	165 ng Eq/mL Geometric Coefficient of Variation 16

SECONDARY outcome

Timeframe: 1 to 8 hours postdose

Population: All enrolled participants.

The metabolites of LY2886721 were identified using a high performance liquid chromatography (HPLC) chromatogram. The relative abundance of LY2886721 and its metabolites in plasma were reported as a percentage of recovered radioactivity and calculated by dividing the sum of the radioactive content of fractions contributing to a particular peak by the sum of the radioactive content of all fractions in the radio chromatogram, then multiplying by 100. Radioactivity corresponds to 80 μCi [^14C]-LY2886721.

Outcome measures

Measure	[^14C]-LY2886721 n=6 Participants Single 25-mg LY2886721 dose containing approximately 80 μCi of \[\^14C\]-LY2886721, administered as an oral solution.
Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Plasma LY2886721 (parent) 1-hour(h) Postdose	42.1 percentage of recovered radioactivity Standard Deviation 9.8
Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Plasma Predominant Metabolite 1h Postdose	18.0 percentage of recovered radioactivity Standard Deviation 6.6
Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Plasma LY2886721 (parent) 2h Postdose	38.3 percentage of recovered radioactivity Standard Deviation 6.4
Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Plasma Predominant Metabolite 2h Postdose	15.7 percentage of recovered radioactivity Standard Deviation 6.5
Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Plasma LY2886721 (parent) 4h Postdose	37.2 percentage of recovered radioactivity Standard Deviation 6.6
Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Plasma Predominant Metabolite 4h Postdose	13.7 percentage of recovered radioactivity Standard Deviation 3.1
Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Plasma LY2886721 (parent) 8h Postdose	39.4 percentage of recovered radioactivity Standard Deviation 12.9
Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Plasma Predominant Metabolite 8h Postdose	15.2 percentage of recovered radioactivity Standard Deviation 2.8

SECONDARY outcome

Timeframe: 0 to 72 hours postdose

Population: All enrolled participants.

The metabolites of LY2886721 were identified using an HPLC chromatogram. The relative abundance of LY2886721 and its metabolites in urine were reported as a percentage of recovered radioactivity and calculated by dividing the sum of the radioactive content of fractions contributing to a particular peak by the sum of the radioactive content of all fractions in the radio chromatogram, then multiplying by 100. Radioactivity corresponds to 80 μCi [^14C]-LY2886721.

Outcome measures

Measure	[^14C]-LY2886721 n=6 Participants Single 25-mg LY2886721 dose containing approximately 80 μCi of \[\^14C\]-LY2886721, administered as an oral solution.
Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Urine LY2886721 (parent)	12.3 percentage of recovered radioactivity Standard Deviation 3.7
Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Urine Predominant Metabolite	36.4 percentage of recovered radioactivity Standard Deviation 3.6

SECONDARY outcome

Timeframe: 0 to 144 hours postdose

Population: All enrolled participants.

The metabolites of LY2886721 were identified using an HPLC chromatogram. The relative abundance of LY2886721 and its metabolites in feces were reported as a percentage of recovered radioactivity and calculated by dividing the sum of the radioactive content of fractions contributing to a particular peak by the sum of the radioactive content of all fractions in the radio chromatogram, then multiplying by 100. Radioactivity corresponds to 80 μCi [^14C]-LY2886721.

Outcome measures

Measure	[^14C]-LY2886721 n=6 Participants Single 25-mg LY2886721 dose containing approximately 80 μCi of \[\^14C\]-LY2886721, administered as an oral solution.
Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Feces LY2886721 (parent)	NA percentage of recovered radioactivity Standard Deviation NA The relative abundance of LY2886721 in feces was not determined because LY2886721 was below the limit of quantitation.
Relative Abundance of LY2886721 and the Metabolites of LY2886721 in Feces Metabolites	4.1 percentage of recovered radioactivity Standard Deviation 2.4

Adverse Events

[^14C]-LY2886721

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]-LY2886721 n=6 participants at risk Single 25-mg LY2886721 dose containing approximately 80 μCi of \[\^14C\]-LY2886721, administered as an oral solution.
General disorders Application site erythema	33.3% 2/6 • Number of events 2
General disorders Vessel puncture site haematoma	16.7% 1/6 • Number of events 1
Nervous system disorders Headache	16.7% 1/6 • Number of events 2

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