Disposition of 14C-LY3009104 Following Oral Administration in Healthy Human Subjects

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01299285
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arm: 1
• Duration (Days): 28
• Patients Per Site Per Month: 6.5

Study Details

Study Description

Brief Summary

This is a single dose study of radiolabeled [14C]-LY3009104 in healthy male volunteers to study the absorption, distribution, metabolism, and elimination of LY3009104. This study requires minimum of 7 days and maximum of 22 days stay. 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: LY3009104	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-LY3009104 Following Oral Administration in Healthy Human Male Subjects
• Study Start Date: Feb 1, 2011
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Mar 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY3009104 Single 10-milligram (mg) oral dose containing 100 microcuries of 14C-labeled LY3009104	Drug: LY3009104; Administered orally; Other Names: Baricitinib

Outcome Measures

Primary Outcome Measures

1. Percentage of the Total Radioactive Dose Administered Excreted From Urine and Feces [Baseline up to 120 hours]

Secondary Outcome Measures

1. Plasma Pharmacokinetics: LY3009104 Area Under the Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] [Baseline up to 48 hours]

2. Plasma Pharmacokinetics: Radioactivity Area Under the Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)] [Baseline up to 48 hours]

3. Plasma Pharmacokinetics: Maximum Observed LY3009104 Concentration (Cmax) [Baseline up to 48 hours]

4. Plasma Pharmacokinetics: Maximum Observed Radioactivity Concentration (Cmax) [Baseline up to 48 hours]

5. Plasma Pharmacokinetics: LY3009104 and Radioactivity Time to Maximum Observed Concentration (Tmax) [Baseline up to 48 hours]

6. Percentage of Dose of LY3009104 and LY3009104 Metabolites in Urine [Baseline up to 48 hours]

   Percentages of LY3009104 (parent) and LY3009104 metabolites that were excreted in the urine are reported. Only those metabolites that were detectable in the urine are included in the report.

7. Percentage of Dose of LY3009104 and LY3009104 Metabolites in Feces [Baseline up to 72 hours]

   Percentages of LY3009104 (parent) and LY3009104 metabolites that were excreted in the feces are reported. Only those metabolites that were detectable in the feces are included in the report.

8. Percentage of Total Radioactivity of LY3009104 and LY3009104 Metabolites in Plasma [Baseline up to 24 hours]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Overtly healthy males, as determined by medical history and physical examination

• Will either be sterile or, if sexually active, agree to use a reliable method of birth control from check-in until 3 months after the end of the study

• Body mass index (BMI) between 19 and 30 kilogram/square meter (kg/m²)

• Experience on average 1 to 2 bowel movements per day

• Clinical laboratory test results within the normal reference range for the clinical research unit (CRU) or, results with acceptable deviations which are judged to be not clinically significant by the investigator

• Normal blood pressure and heart rate (sitting) as determined by the investigator

• Venous access sufficient to allow blood sampling

• Are reliable and willing to make themselves available for the duration of the study, and are willing to abide by the CRU policies and procedures, and study restrictions

• Have given written informed consent approved by Lilly and the Institutional Review Board (IRB) governing the CRU

Exclusion Criteria:

• Are currently enrolled in, have completed or discontinued, a clinical trial involving an investigational product or are concurrently enrolled in any other type of medical research judged not to be scientifically, or medically compatible with this study

• Have known allergies to LY3009104, related compounds, or any components of the formulation

• Have previously received the investigational product in this study, have completed or withdrawn from this study or any other study investigating LY3009104

• History or presence of an abnormality in the 12-lead electrocardiogram (ECG) that, in the opinion of the investigator, is clinically significant

• Current or recent history (<30 days prior to Screening and/or <45 days prior to Check-in) of a clinically significant bacterial, fungal, parasitic, viral (not including rhinopharyngitis), or mycobacterial infection

• An Absolute Neutrophil Count (ANC) less than 2000 cells/microliter. For abnormal values a single repeat will be allowed

• 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

• Show evidence of significant active neuropsychiatric disease and in particular evidence of significant medical or psychiatric illness within the past 12 months

• Have known substance dependence or abuse within 6 months prior to the study (according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV] diagnosis), or regularly use known drugs of abuse and/or show positive findings on urinary drug screening

• Show evidence of human immunodeficiency virus (HIV) infection and/or positive human HIV antibodies

• Show evidence of hepatitis C and/or positive hepatitis C antibody

• Evidence hepatitis B (active or surface antigen positive [HBsAg+]) or hepatitis B core antibody positive, hepatitis B surface antibody negative (HBcAb+, HBsAb-)

• Use of prescription medication; over-the-counter medication; or herbal preparations containing St. John's Wort, kava, garlic, ginger, gingko biloba, or guarana within 14 days prior to admission

• Consumption of grapefruit or grapefruit-containing foods or juices within 7 days prior to dosing or at any time during the study

• Have an average weekly alcohol intake that exceeds 15 units per week, or are unwilling to stop alcohol consumption for the duration of the study (1 unit = 12 oz or 360 milliliter (mL) of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits)

• Consume 5 or more cups of coffee (or other beverages of comparable caffeine content) per day, on a habitual basis, or any subjects unwilling to adhere to study caffeine restrictions (no caffeine 48 hours prior to admission until the end of study

• Use of tobacco or nicotine-replacement products within the 6 months prior to study entry or at any time during the study

• Have donated blood of more than 500 mL within the last month

• Have participated in a 14C-study within the last 6 months prior to Check-in for this study. The total exposure from this study and the previous study must be within the Code of Federal Regulations (CFR) recommended levels considered safe (per 21 CFR 361.1), for example less than 5,000 millirem (mrem)/year whole body annual exposure

• 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)

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, 9AM to 5PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Madison	Wisconsin	United States

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, 9AM - 5PM 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: NCT01299285
• Other Study ID Numbers: 14010; I4V-MC-JADG
• First Posted: Feb 18, 2011
• Last Update Posted: Jun 8, 2017
• Last Verified: May 1, 2017

• Keywords provided by Eli Lilly and Company: Absorption; Distribution; Metabolism; Excretion; Mass balance; Metabolic profile; Radiolabeled study; 14C

Study Results

Participant Flow

Arm/Group Title	LY3009104 (Baricitinib)
Arm/Group Description	Single 10-milligram (mg) oral dose containing 100 microcuries of 14C-labeled LY3009104
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	LY3009104
Arm/Group Description	Single 10-mg oral dose containing 100 microcuries of 14C-labeled LY3009104
Overall Participants	6
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.7 (11.3)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	6 100%
Race/Ethnicity, Customized (participants) [Number]
Asian	1 16.7%
White	5 83.3%
Region of Enrollment (participants) [Number]
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of the Total Radioactive Dose Administered Excreted From Urine and Feces
Time Frame	Baseline up to 120 hours

Outcome Measure Data

Analysis Population Description

Participants who took study drug.

Arm/Group Title	LY3009104
Arm/Group Description	Single 10-mg oral dose containing 100 microcuries of 14C-labeled LY3009104
Measure Participants	6
Urine	75.2 (6.74)
Feces	19.9 (4.92)

2. Secondary Outcome

Title	Plasma Pharmacokinetics: LY3009104 Area Under the Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)]
Time Frame	Baseline up to 48 hours

Outcome Measure Data

Analysis Population Description

Participants who took study drug.

Arm/Group Title	LY3009104
Arm/Group Description	Single 10-mg oral dose containing 100 microcuries of 14C-labeled LY3009104
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [hour*nanomoles/liter(h*nmol/L)]	1570 (28)

3. Secondary Outcome

Title	Plasma Pharmacokinetics: Radioactivity Area Under the Concentration-Time Curve From Time Zero to Infinity [AUC(0-∞)]
Time Frame	Baseline up to 48 hours

Outcome Measure Data

Analysis Population Description

Participants who took study drug.

Arm/Group Title	LY3009104
Arm/Group Description	Single 10-mg oral dose containing 100 microcuries of 14C-labeled LY3009104
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [hour*nanomole-equivalents/kilogram]	1530 (31)

4. Secondary Outcome

Title	Plasma Pharmacokinetics: Maximum Observed LY3009104 Concentration (Cmax)
Time Frame	Baseline up to 48 hours

Outcome Measure Data

Analysis Population Description

Participants who took study drug.

Arm/Group Title	LY3009104
Arm/Group Description	Single 10-mg oral dose containing 100 microcuries of 14C-labeled LY3009104
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [nanomoles/liter (nmol/L)]	227 (36)

5. Secondary Outcome

Title	Plasma Pharmacokinetics: Maximum Observed Radioactivity Concentration (Cmax)
Time Frame	Baseline up to 48 hours

Outcome Measure Data

Analysis Population Description

Participants who took study drug.

Arm/Group Title	LY3009104
Arm/Group Description	Single 10-mg oral dose containing 100 microcuries of 14C-labeled LY3009104
Measure Participants	6
Geometric Mean (Geometric Coefficient of Variation) [nanomole-equivalents/milliliter]	231 (35)

6. Secondary Outcome

Title	Plasma Pharmacokinetics: LY3009104 and Radioactivity Time to Maximum Observed Concentration (Tmax)
Time Frame	Baseline up to 48 hours

Outcome Measure Data

Analysis Population Description

Participants who took study drug.

Arm/Group Title	LY3009104
Arm/Group Description	Single 10-mg oral dose containing 100 microcuries of 14C-labeled LY3009104
Measure Participants	6
LY3009104	1.00
Radioactivity	1.00

7. Secondary Outcome

Title	Percentage of Dose of LY3009104 and LY3009104 Metabolites in Urine
Description	Percentages of LY3009104 (parent) and LY3009104 metabolites that were excreted in the urine are reported. Only those metabolites that were detectable in the urine are included in the report.
Time Frame	Baseline up to 48 hours

Outcome Measure Data

Analysis Population Description

Participants who took study drug.

Arm/Group Title	LY3009104
Arm/Group Description	Single 10-mg oral dose containing 100 microcuries of 14C-labeled LY3009104
Measure Participants	6
LY3009104	68.5
Metabolite M3	0.9
Metabolite M10	1.0
Metabolite M22	3.2

8. Secondary Outcome

Title	Percentage of Dose of LY3009104 and LY3009104 Metabolites in Feces
Description	Percentages of LY3009104 (parent) and LY3009104 metabolites that were excreted in the feces are reported. Only those metabolites that were detectable in the feces are included in the report.
Time Frame	Baseline up to 72 hours

Outcome Measure Data

Analysis Population Description

Participants who took study drug.

Arm/Group Title	LY3009104
Arm/Group Description	Single 10-mg oral dose containing 100 microcuries of 14C-labeled LY3009104
Measure Participants	6
LY3009104	14.8
Metabolite M12	0.9

9. Secondary Outcome

Title	Percentage of Total Radioactivity of LY3009104 and LY3009104 Metabolites in Plasma
Time Frame	Baseline up to 24 hours

Outcome Measure Data

Analysis Population Description

Participants who took study drug.

Arm/Group Title	LY3009104	LY3009104 Metabolites
Arm/Group Description	The percentage of total radioactivity of LY3009104 (parent) in the plasma after receiving a single 10-mg oral dose containing 100 microcuries of 14C-labeled LY3009104	The percentage of total radioactivity of all LY3009104 metabolites in the plasma after receiving a single 10-mg oral dose containing 100 microcuries of 14C-labeled LY3009104
Measure Participants	6	6
1 hour	92.3	0
2 hour	94.5	0
4 hour	97.0	0
8 hour	91.2	0
24 hour	0	0

Adverse Events

Arm/Group Title	LY3009104
Arm/Group Description	Single 10-mg oral dose containing 100 microcuries of 14C-labeled LY3009104
All Cause Mortality
	LY3009104
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	LY3009104
	Affected / at Risk (%)	# Events
Total	0/6 (0%)
Other (Not Including Serious) Adverse Events
	LY3009104
	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)
Eye disorders
Ocular hyperaemia	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.