A Study of Carbon-14-Labeled LY2835219 ([^14C]-LY2835219) in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01913314
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Months): 2
• Patients Per Site Per Month: 3

Study Details

Study Description

Brief Summary

This type of study is called a radiolabeled study. For this study, LY2835219 (study drug) has been specially prepared to contain radiolabeled carbon [^14C]. [^14C] is a naturally occurring radioactive form of the element carbon. This study will help understand how the drug appears in the blood, urine, and stool after it is administered.

In addition, this study will also evaluate the safety and tolerability of a single dose of LY2835219 when given to healthy participants. Information about any side effects that may occur will also be collected.

This study will last about 3 weeks for each participant, not including screening.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: [^14C]-LY2835219	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: Basic Science
• Official Title: Disposition of [^14C]-LY2835219 Following Oral Administration in Healthy Subjects
• Study Start Date: Aug 1, 2013
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: [^14C]-LY2835219 Single 150 milligram (mg) oral dose solution of LY2835219 containing 5 micro-curies of (µCi) [^14C] labeled drug	Drug: [^14C]-LY2835219; Administered as oral solution; Other Names: abemaciclib

Outcome Measures

Primary Outcome Measures

1. Urinary and Fecal Excretion of LY2835219-Related Radioactivity Over Time Expressed as a Percentage of the Total Radioactive Dose Administered [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]

   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.

Secondary Outcome Measures

1. Plasma Pharmacokinetics (PK) of LY2835219 and Metabolite of LY2835219: Maximum Observed Concentration (Cmax) [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]

2. Plasma PK of Radioactivity: Cmax [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]

3. Plasma PK of LY2835219, Metabolite of LY2835219, and Radioactivity: Time of Maximum Observed Concentration (Tmax) [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]

4. 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)] [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]

5. Plasma PK of Radioactivity: AUC(0 to Tlast) [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]

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

6. Plasma PK of LY2835219 and Metabolite of LY2835219: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] [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]

7. Plasma PK of Radioactivity: AUC(0-∞) [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]

8. Relative Abundance of LY2835219 and Metabolites of LY2835219 Eliminated in Urine and Feces [Predose through 216 h postdose; Fecal samples collected at 24-h intervals]

   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.

9. Relative Abundance of LY2835219 and Metabolites of LY2835219 in Plasma [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]

   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.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Overtly healthy male or female participants as determined by medical history and physical examination

• Male participants will be sterile

• Female participants will be surgically sterile or postmenopausal

• Have a body mass index (BMI) of 18 to 29 kilograms per square meter (kg/m^2)

• Have venous access sufficient to allow for blood sampling

Exclusion Criteria:

• Have a history or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; of constituting a risk when taking the study medication; or of interfering with the interpretation of data

• Gastrointestinal disorders causing clinically significant symptoms such as nausea, vomiting, and diarrhea, or malabsorption syndromes

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: NCT01913314
• Other Study ID Numbers: 14930; I3Y-MC-JPBD
• First Posted: Aug 1, 2013
• Last Update Posted: Jan 7, 2019
• Last Verified: Dec 1, 2018

Study Results

Participant Flow

Arm/Group Title	[^14C]-LY2835219
Arm/Group Description	Single 150-milligram (mg) LY2835219 dose containing 5 micro- curies (µCi) of carbon-14-labeled LY2835219 ([^14C]-LY2835219), 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]-LY2835219
Arm/Group Description	Single 150-mg LY2835219 dose containing 5 µCi of [^14C]-LY2835219, administered as an oral solution.
Overall Participants	6
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	6 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	3 50%
Male	3 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 16.7%
Not Hispanic or Latino	5 83.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	6 100%
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	Urinary and Fecal Excretion of LY2835219-Related 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 or feces = (amount of radioactive dose recovered in urine or feces / total radioactive dose administered) * 100.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Participants who received study drug.

Arm/Group Title	[^14C]-LY2835219
Arm/Group Description	Single 150-mg LY2835219 dose containing 5 µCi of [^14C]-LY2835219, administered as an oral solution.
Measure Participants	6
Urine	3.43 (2.20)
Feces	81.0 (6.71)

2. Secondary Outcome

Title	Plasma Pharmacokinetics (PK) of LY2835219 and Metabolite of LY2835219: Maximum Observed Concentration (Cmax)
Time Frame	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

Outcome Measure Data

Analysis Population Description

Participants who received study drug and had evaluable PK data.

Arm/Group Title	[^14C]-LY2835219
Arm/Group Description	Single 150-mg LY2835219 dose containing 5 µCi of [^14C]-LY2835219, administered as an oral solution.
Measure Participants	6
LY2835219	63.7 (49)
M20	30.9 (19)

3. Secondary Outcome

Title	Plasma PK of Radioactivity: Cmax
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	[^14C]-LY2835219
Arm/Group Description	Single 150-mg LY2835219 dose containing 5 µCi of [^14C]-LY2835219, administered as an oral solution.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram equivalents per gram (ng Eq/g)]	123 (27)

4. Secondary Outcome

Title	Plasma PK of LY2835219, Metabolite of LY2835219, and Radioactivity: Time of Maximum Observed Concentration (Tmax)
Time Frame	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

Outcome Measure Data

Analysis Population Description

Participants who received study drug and evaluable PK tmax data.

Arm/Group Title	[^14C]-LY2835219
Arm/Group Description	Single 150-mg LY2835219 dose containing 5 µCi of [^14C]-LY2835219, administered as an oral solution.
Measure Participants	6
LY2835219	8.00
M20	8.00
Total Radioactivity	8.00

5. Secondary Outcome

Title	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)]
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	[^14C]-LY2835219
Arm/Group Description	Single 150-mg LY2835219 dose containing 5 µCi of [^14C]-LY2835219, administered as an oral solution.
Measure Participants	6
LY2835219	2310 (85)
M20	1760 (43)

6. Secondary Outcome

Title	Plasma PK of Radioactivity: AUC(0 to Tlast)
Description	The PK of radioactivity was measured as nanogram equivalents times hours per gram (ng Eq*h/g).
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	[^14C]-LY2835219
Arm/Group Description	Single 150-mg LY2835219 dose containing 5 µCi of [^14C]-LY2835219, administered as an oral solution.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng Eq*h/g]	6580 (41)

7. Secondary Outcome

Title	Plasma PK of LY2835219 and Metabolite of LY2835219: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)]
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	[^14C]-LY2835219
Arm/Group Description	Single 150-mg LY2835219 dose containing 5 µCi of [^14C]-LY2835219, administered as an oral solution.
Measure Participants	6
LY2835219	2370 (83)
M20	1830 (42)

8. Secondary Outcome

Title	Plasma PK of Radioactivity: AUC(0-∞)
Time Frame	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

Outcome Measure Data

Analysis Population Description

Participants who received study drug and had evaluable PK data.

Arm/Group Title	[^14C]-LY2835219
Arm/Group Description	Single 150-mg LY2835219 dose containing 5 µCi of [^14C]-LY2835219, administered as an oral solution.
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [ng Eq*h/g]	7010 (42)

9. Secondary Outcome

Title	Relative Abundance of LY2835219 and Metabolites of LY2835219 Eliminated in Urine and Feces
Description	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.
Time Frame	Predose through 216 h postdose; Fecal samples collected at 24-h intervals

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	[^14C]-LY2835219
Arm/Group Description	Single 150-mg LY2835219 dose containing 5 µCi of [^14C]-LY2835219, administered as an oral solution.
Measure Participants	6
LY2835219	7
Metabolites	52

10. Secondary Outcome

Title	Relative Abundance of LY2835219 and Metabolites of LY2835219 in Plasma
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	[^14C]-LY2835219
Arm/Group Description	Single 150-mg LY2835219 dose containing 5 µCi of [^14C]-LY2835219, administered as an oral solution.
Measure Participants	6
LY2835219	34
Metabolites	44

Adverse Events

Arm/Group Title	[^14C]-LY2835219
Arm/Group Description	Single 150-mg LY2835219 dose containing 5 µCi of [^14C]-LY2835219, administered as an oral solution.
All Cause Mortality
	[^14C]-LY2835219
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	[^14C]-LY2835219
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	[^14C]-LY2835219
	Affected / at Risk (%)	# Events
Total	4/6 (66.7%)
General disorders
Vessel Puncture Site Haematoma	2/6 (33.3%)	2
Vessel Puncture Site Pain	1/6 (16.7%)	1
Vessel Puncture Site Swelling	1/6 (16.7%)	1
Infections and infestations
Folliculitis	1/6 (16.7%)	1
Injury, poisoning and procedural complications
Excoriation	1/6 (16.7%)	1
Musculoskeletal and connective tissue disorders
Pain in Extremity	1/6 (16.7%)	1
Nervous system disorders
Headache	1/6 (16.7%)	1
Respiratory, thoracic and mediastinal disorders
Choking	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.