A Pharmacokinetic Study of Baricitinib in Participants With Liver Disease

• ClinicalTrials.gov Identifier: NCT01870388
• Recruitment Status: Completed
• First Posted: June 6, 2013
• Results First Posted: April 21, 2017
• Last Update Posted: June 6, 2017
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Conditions: Liver Diseases; Hepatic Insufficiency
• Intervention: Drug: Baricitinib
• Enrollment: 16

Participant Flow

Recruitment Details
Pre-assignment Details	An interim analysis was to be performed after ≤6 participants (pts) each in Group (G) 1 and G2 completed the study. If a <1.3-fold difference in exposure was seen between pts with moderate hepatic impairment (G2) and pts with normal hepatic function (G1), then pts with mild hepatic impairment (G3) were not to be enrolled. No pt was enrolled in G3.

Arm/Group Title	Baricitinib (Healthy Participants)	Baricitinib (Moderate Hepatic Impairment)
Arm/Group Description	Group 1: A single 4-milligram (mg) dose of baricitinib (one 4-mg tablet) administered once, orally, to participants with normal hepatic function.	Group 2: A single 4-mg dose of baricitinib (one 4-mg tablet) administered once, orally, to participants with moderate hepatic impairment as classified by Child-Pugh B.
Period Title: Overall Study
Started	8	8
Received 1 Dose of Study Drug	8	8
Completed	8	8
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Baricitinib (Healthy Participants)	Baricitinib (Moderate Hepatic Impairment)	Total
Arm/Group Description		Group 1: A single 4-mg dose of baricitinib (one 4-mg tablet) administered once, orally, to participants with normal hepatic function.	Group 2: A single 4-mg dose of baricitinib (one 4-mg tablet) administered once, orally, to participants with moderate hepatic impairment as classified by Child-Pugh B.	Total of all reporting groups
Overall Number of Baseline Participants		8	8	16
Baseline Analysis Population Description		All enrolled participants.
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants	8 participants	16 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	6 75.0%	8 100.0%	14 87.5%
	>=65 years	2 25.0%	0 0.0%	2 12.5%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants	8 participants	16 participants
	Female	1 12.5%	1 12.5%	2 12.5%
	Male	7 87.5%	7 87.5%	14 87.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants	8 participants	16 participants
	Hispanic or Latino	5 62.5%	3 37.5%	8 50.0%
	Not Hispanic or Latino	3 37.5%	5 62.5%	8 50.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	8 participants	8 participants	16 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 12.5%	0 0.0%	1 6.3%
	White	7 87.5%	8 100.0%	15 93.8%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	8 participants	8 participants	16 participants
		8	8	16

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Concentration (Cmax) of Baricitinib (LY3009104)
Description	[Not Specified]
Time Frame	Predose up to 48 hours (h) postdose

Outcome Measure Data

Analysis Population Description

Participants who received 1 dose of study drug and had evaluable PK data.

Arm/Group Title	Baricitinib (Healthy Participants)	Baricitinib (Moderate Hepatic Impairment)
Arm/Group Description:	Group 1: A single 4-mg dose of baricitinib (one 4-mg tablet) administered once, orally to participants with normal hepatic function.	Group 2: A single 4-mg dose of baricitinib (one 4-mg tablet) administered once, orally to participants with moderate hepatic impairment as classified by Child-Pugh B.
Overall Number of Participants Analyzed	8	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanograms per milliliter (ng/mL)
	35.3; (25%)	38.2; (23%)

2. Primary Outcome

Title	PK: Area Under the Concentration Versus Time Curve From Zero to Infinity [AUC(0-∞)] of Baricitinib
Description	[Not Specified]
Time Frame	Predose up to 48 h postdose

Outcome Measure Data

Analysis Population Description

Participants who received 1 dose of study drug and had evaluable PK data.

Arm/Group Title	Baricitinib (Healthy Participants)	Baricitinib (Moderate Hepatic Impairment)
Arm/Group Description:	Group 1: A single 4-mg dose of baricitinib (one 4-mg tablet) administered once, orally, to participants with normal hepatic function.	Group 2: A single 4-mg dose of baricitinib (one 4-mg tablet) administered once, orally, to participants with moderate hepatic impairment as classified by Child-Pugh B.
Overall Number of Participants Analyzed	8	8
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: nanograms*hour/milliliter (ng*h/mL)
	295; (25%)	350; (28%)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Baricitinib (Healthy Participants)		Baricitinib (Moderate Hepatic Impairment)
Arm/Group Description	Group 1: A single 4-mg dose of baricitinib (one 4-mg tablet) administered once, orally, to participants with normal hepatic function.		Group 2: A single 4-mg dose of baricitinib (one 4-mg tablet) administered once, orally, to participants with moderate hepatic impairment as classified by Child-Pugh B.
All-Cause Mortality
	Baricitinib (Healthy Participants)		Baricitinib (Moderate Hepatic Impairment)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Baricitinib (Healthy Participants)		Baricitinib (Moderate Hepatic Impairment)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0.00%)		0/8 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Baricitinib (Healthy Participants)		Baricitinib (Moderate Hepatic Impairment)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/8 (25.00%)		4/8 (50.00%)
Gastrointestinal disorders
Nausea † 1	0/8 (0.00%)	0	1/8 (12.50%)	1
Investigations
Neutrophil count decreased † 1	0/8 (0.00%)	0	1/8 (12.50%)	1
Nervous system disorders
Dizziness † 1	1/8 (12.50%)	1	1/8 (12.50%)	1
Headache † 1	1/8 (12.50%)	1	1/8 (12.50%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 16.0

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Chief Medical Officer
• Organization: Eli Lilly and Company
• Phone: 800-545-5979

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01870388
• Other Study ID Numbers: 14600; I4V-MC-JAGC ( Other Identifier: Eli Lilly and Company )
• First Submitted: June 3, 2013
• First Posted: June 6, 2013
• Results First Submitted: March 10, 2017
• Results First Posted: April 21, 2017
• Last Update Posted: June 6, 2017