Trial Outcomes & Findings for A Study of Carbon-14-Labeled LY2835219 ([^14C]-LY2835219) in Healthy Participants (NCT NCT01913314)

NCT ID: NCT01913314

Last Updated: 2019-01-07

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 6 participants
• Primary outcome timeframe: Predose up to Day 14 postdose; Fecal samples collected at 24-hour (h) intervals; Urine collected at 0 to 6 h, 6 to 12 h, and 12 to 24 h postdose and at 24-h intervals thereafter up to Day 14 postdose
• Results posted on: 2019-01-07

Participant Flow

Participant milestones

Measure	[^14C]-LY2835219 Single 150-milligram (mg) LY2835219 dose containing 5 micro- curies (µCi) of carbon-14-labeled LY2835219 (\[\^14C\]-LY2835219), 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 Carbon-14-Labeled LY2835219 ([^14C]-LY2835219) in Healthy Participants

Baseline characteristics by cohort

Measure	[^14C]-LY2835219 n=6 Participants Single 150-mg LY2835219 dose containing 5 µCi of \[\^14C\]-LY2835219, administered as an oral solution.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	3 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	0 Participants n=5 Participants
Race (NIH/OMB) White	6 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 Day 14 postdose; Fecal samples collected at 24-hour (h) intervals; Urine collected at 0 to 6 h, 6 to 12 h, and 12 to 24 h postdose and at 24-h intervals thereafter up to Day 14 postdose

Population: Participants who received study drug.

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

Outcome measures

Measure	[^14C]-LY2835219 n=6 Participants Single 150-mg LY2835219 dose containing 5 µCi of \[\^14C\]-LY2835219, administered as an oral solution.
Urinary and Fecal Excretion of LY2835219-Related Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered Urine	3.43 percentage radioactive dose administered Standard Deviation 2.20
Urinary and Fecal Excretion of LY2835219-Related Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered Feces	81.0 percentage radioactive dose administered Standard Deviation 6.71

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose

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

Outcome measures

Measure	[^14C]-LY2835219 n=6 Participants Single 150-mg LY2835219 dose containing 5 µCi of \[\^14C\]-LY2835219, administered as an oral solution.
Plasma Pharmacokinetics (PK) of LY2835219 and Metabolite of LY2835219: Maximum Observed Concentration (Cmax) M20	30.9 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 19
Plasma Pharmacokinetics (PK) of LY2835219 and Metabolite of LY2835219: Maximum Observed Concentration (Cmax) LY2835219	63.7 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 49

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose

Population: Participants who received study drug and had evaluable PK Cmax data.

Outcome measures

Measure	[^14C]-LY2835219 n=6 Participants Single 150-mg LY2835219 dose containing 5 µCi of \[\^14C\]-LY2835219, administered as an oral solution.
Plasma PK of Radioactivity: Cmax	123 nanogram equivalents per gram (ng Eq/g) Geometric Coefficient of Variation 27

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose

Population: Participants who received study drug and evaluable PK tmax data.

Outcome measures

Measure	[^14C]-LY2835219 n=6 Participants Single 150-mg LY2835219 dose containing 5 µCi of \[\^14C\]-LY2835219, administered as an oral solution.
Plasma PK of LY2835219, Metabolite of LY2835219, and Radioactivity: Time of Maximum Observed Concentration (Tmax) LY2835219	8.00 h Interval 6.0 to 8.0
Plasma PK of LY2835219, Metabolite of LY2835219, and Radioactivity: Time of Maximum Observed Concentration (Tmax) M20	8.00 h Interval 6.0 to 10.0
Plasma PK of LY2835219, Metabolite of LY2835219, and Radioactivity: Time of Maximum Observed Concentration (Tmax) Total Radioactivity	8.00 h Interval 6.0 to 10.0

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose

Population: Participants who received study drug and had evaluable PK AUC(0-tlast) data.

Outcome measures

Measure	[^14C]-LY2835219 n=6 Participants Single 150-mg LY2835219 dose containing 5 µCi of \[\^14C\]-LY2835219, administered as an oral solution.
Plasma PK of LY2835219 and Metabolite of LY2835219: Area Under the Concentration-Time Curve From Time Zero to the Last Time Point With a Measurable Concentration [AUC(0-tlast)] LY2835219	2310 nanograms*hour/milliliter (ng*h/mL) Geometric Coefficient of Variation 85
Plasma PK of LY2835219 and Metabolite of LY2835219: Area Under the Concentration-Time Curve From Time Zero to the Last Time Point With a Measurable Concentration [AUC(0-tlast)] M20	1760 nanograms*hour/milliliter (ng*h/mL) Geometric Coefficient of Variation 43

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose

Population: Participants who received study drug and had evaluable PK AUC(0-tlast) data.

The PK of radioactivity was measured as nanogram equivalents times hours per gram (ng Eq*h/g).

Outcome measures

Measure	[^14C]-LY2835219 n=6 Participants Single 150-mg LY2835219 dose containing 5 µCi of \[\^14C\]-LY2835219, administered as an oral solution.
Plasma PK of Radioactivity: AUC(0 to Tlast)	6580 ng Eq*h/g Geometric Coefficient of Variation 41

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose

Population: Participants who received study drug and had evaluable PK AUC(0-∞) data.

Outcome measures

Measure	[^14C]-LY2835219 n=6 Participants Single 150-mg LY2835219 dose containing 5 µCi of \[\^14C\]-LY2835219, administered as an oral solution.
Plasma PK of LY2835219 and Metabolite of LY2835219: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] LY2835219	2370 ng*h/mL Geometric Coefficient of Variation 83
Plasma PK of LY2835219 and Metabolite of LY2835219: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] M20	1830 ng*h/mL Geometric Coefficient of Variation 42

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose

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

Outcome measures

Measure	[^14C]-LY2835219 n=6 Participants Single 150-mg LY2835219 dose containing 5 µCi of \[\^14C\]-LY2835219, administered as an oral solution.
Plasma PK of Radioactivity: AUC(0-∞)	7010 ng Eq*h/g Geometric Coefficient of Variation 42

SECONDARY outcome

Timeframe: Predose through 216 h postdose; Fecal samples collected at 24-h intervals

Population: Participants who received study drug and had evaluable PK data. No participants were analyzed for relative abundance of LY2835219 and metabolites of LY2835219 in urine.

The abundance (as percentage dose) of LY2835219 or its metabolites eliminated in feces is calculated as = (amount of LY2835219 or its metabolites recovered in feces / total amount administered) * 100. Due to low radioactivity of dose recovered in urine, further quantitative profiling of urine was not conducted.

Outcome measures

Measure	[^14C]-LY2835219 n=6 Participants Single 150-mg LY2835219 dose containing 5 µCi of \[\^14C\]-LY2835219, administered as an oral solution.
Relative Abundance of LY2835219 and Metabolites of LY2835219 Eliminated in Urine and Feces LY2835219	7 percentage of radioactive dose excreted
Relative Abundance of LY2835219 and Metabolites of LY2835219 Eliminated in Urine and Feces Metabolites	52 percentage of radioactive dose excreted

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h postdose, thereafter at 24-h intervals up to Day 14 postdose

Population: Participants who received study drug and had evaluable PK AUC(0-∞) data.

The relative abundance of LY2835219 or its metabolites in plasma were estimated based on AUC(0-∞) and reported as a percentage of total plasma radioactivity. The relative abundance of LY2835219 or its metabolites calculated as = [AUC (0-∞) of LY2835219 or its metabolites in plasma / AUC (0-∞) of total plasma radioactivity] * 100.

Outcome measures

Measure	[^14C]-LY2835219 n=6 Participants Single 150-mg LY2835219 dose containing 5 µCi of \[\^14C\]-LY2835219, administered as an oral solution.
Relative Abundance of LY2835219 and Metabolites of LY2835219 in Plasma LY2835219	34 percentage of total plasma radioactivity
Relative Abundance of LY2835219 and Metabolites of LY2835219 in Plasma Metabolites	44 percentage of total plasma radioactivity

Adverse Events

[^14C]-LY2835219

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	[^14C]-LY2835219 n=6 participants at risk Single 150-mg LY2835219 dose containing 5 µCi of \[\^14C\]-LY2835219, administered as an oral solution.
General disorders Vessel Puncture Site Haematoma	33.3% 2/6 • Number of events 2
General disorders Vessel Puncture Site Pain	16.7% 1/6 • Number of events 1
General disorders Vessel Puncture Site Swelling	16.7% 1/6 • Number of events 1
Infections and infestations Folliculitis	16.7% 1/6 • Number of events 1
Injury, poisoning and procedural complications Excoriation	16.7% 1/6 • Number of events 1
Musculoskeletal and connective tissue disorders Pain in Extremity	16.7% 1/6 • Number of events 1
Nervous system disorders Headache	16.7% 1/6 • Number of events 1
Respiratory, thoracic and mediastinal disorders Choking	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