A Study of Baricitinib and Probenecid in Healthy Participants

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01937026
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 2
• Duration (Months): 2
• Patients Per Site Per Month: 9

Study Details

Study Description

Brief Summary

The purposes of this study are to assess how the body handles baricitinib when it is given with another drug called probenecid. The study doctor will measure the amount of baricitinib that is absorbed into the blood stream and the time that it takes to remove baricitinib from the body. The safety and tolerability of these drugs will be studied. The study will last about 18 days from the first dose to the end of the study (not including screening).

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: Baricitinib; Drug: Probenecid	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Study to Investigate the Potential Impact of Organic Anion Transporter 3 Inhibition by Probenecid on the Pharmacokinetics of Baricitinib (LY3009104) in Healthy Subjects
• Study Start Date: Sep 1, 2013
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Nov 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Baricitinib Single oral dose of 4 milligrams (mg) baricitinib on Day 1	Drug: Baricitinib; Administered orally
Experimental: Baricitinib + Probenecid Oral doses of 1000 mg probenecid once daily on Days 3 through 7, with a single oral dose of 4 mg baricitinib co-administered on Day 5	Drug: Baricitinib; Administered orally; Drug: Probenecid; Administered orally

Outcome Measures

Primary Outcome Measures

1. Pharmacokinetics (PK): Maximum Concentration (Cmax) of Baricitinib [Days 1 and 5: predose of baricitinib, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 and 72 (Day 5 dosing only) hours postdose]

2. PK: Area Under the Concentration Curve From Time 0 to Infinity [AUC (0-∞)] of Baricitinib [Days 1 and 5: predose of baricitinib, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 and 72 (Day 5 dosing only) hours postdose]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Male participants: agree to use 2 reliable methods of birth control with female partners of childbearing potential during the study and for at least 3 months following the last dose of study drug

• Female participants: women not of childbearing potential due to surgical sterilization confirmed by medical history or menopause

• Have a body mass index of 18.0 to 29.0 kilograms per meter square (kg/m^2), inclusive

• Have clinical laboratory test results within the normal reference range

• Have normal renal function

• Have normal blood pressure and pulse rate

Exclusion Criteria:

• Are currently enrolled in a clinical trial or are concurrently enrolled in any other type of medical research

• Have completed or discontinued within the last 90 days from a clinical trial involving a study drug

• Are participants who have previously completed or withdrawn from this study or any other study investigating baricitinib, and have previously received baricitinib

• Have known allergies to baricitinib, probenecid, related compounds, or any components of the baricitinib or probenecid formulations, or history of significant atopy

• Have an abnormality in the 12-lead electrocardiogram (ECG)

• Have a history of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs;

• Have a history of or current gout or gouty arthritis

• Regularly use known drugs of abuse and/or show positive findings on urinary drug screening

• Have a current or recent history of a clinically significant bacterial, fungal, parasitic, viral, or mycobacterial infection

• Have had symptomatic herpes zoster or herpes simplex infection within 90 days prior to the first dose

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

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

• Show evidence of hepatitis B infection and/or positive hepatitis B surface antigen

• Are women who are lactating

• Intend to use over-the-counter or prescription medication (including salicylate drugs) and/or herbal supplements within 14 days prior to dosing and during the study or intended use of vitamin supplements from first dose of study drug until discharge from the Clinical Research Unit (CRU)

• Have consumed or intend to consume grapefruit or grapefruit-containing products within 7 days prior to the first dose and throughout the study

• Have used or intend to use any drugs or substances that are known to be substrates, inhibitors, or inducers of organic anion transporter (OAT)3 or cytochrome P450 (CYP) 3A4

• Have donated or lost blood of more than 500 milliliter (mL) within the last 3 months

• Have an average weekly alcohol intake that exceeds 28 units per week (males) and 21 units per week (females), or are unwilling to stop alcohol consumption from 48 hours prior to the first dose until discharge from the CRU at the end of study

• History of, in the opinion of the investigator, excessive methylxanthine use within the previous 6 months, such as greater than (>) 6 cups of coffee (or equivalent) per day

• Currently smoke more than 10 cigarettes per day

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.	Leeds	West Yorkshire	United Kingdom	LS2 9LH

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: NCT01937026
• Other Study ID Numbers: 14604; I4V-MC-JAGG
• First Posted: Sep 9, 2013
• Last Update Posted: Jun 6, 2017
• Last Verified: May 1, 2017

• Additional relevant MeSH terms: Probenecid

Study Results

Participant Flow

Pre-assignment Detail	This was an open-label, 2-period, fixed-sequence study.

Arm/Group Title	Baricitinib
Arm/Group Description	4 milligram (mg) baricitinib tablet administered orally, once, on Day 1 in Period 1 and on Day 5 in Period 2. 1000 mg probenecid tablet administered orally, twice daily (BID), on Days 3 through 7 in Period 2.
Period Title: Period 1 (Day 1 Through Predose Day 3)
STARTED	18
Received Baricitinib	18
COMPLETED	18
NOT COMPLETED	0
Period Title: Period 1 (Day 1 Through Predose Day 3)
STARTED	18
Received Baricitinib	18
Received Probenecid on Days 3 Through 7	18
COMPLETED	18
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Baricitinib
Arm/Group Description	4 mg baricitinib tablet administered orally, once, on Day 1 in Period 1 and on Day 5 in Period 2. 1000 mg probenecid tablet administered orally, BID, on Days 3 through 7 in Period 2.
Overall Participants	18
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	37.3 (13.3)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	18 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	18 100%
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	18 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United Kingdom	18 100%

Outcome Measures

1. Primary Outcome

Title	Pharmacokinetics (PK): Maximum Concentration (Cmax) of Baricitinib
Time Frame	Days 1 and 5: predose of baricitinib, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 and 72 (Day 5 dosing only) hours postdose

Outcome Measure Data

Analysis Population Description

All enrolled participants who received study drug (baricitinib in Period 1 and baricitinib + probenecid in Period 2) and had PK data to calculate Cmax of baricitinib.

Arm/Group Title	Baricitinib	Baricitinib + Probenecid
Arm/Group Description	4 mg baricitinib tablet administered orally, once, on Day 1 in Period 1.	4 mg baricitinib tablet administered orally, once, on Day 5 in Period 2. 1000 mg probenecid tablet administered orally, BID, on Days 3 through 7 in Period 2.
Measure Participants	18	18
Geometric Mean (Geometric Coefficient of Variation) [nanograms/milliliter (ng/mL)]	36.2 (22)	37.3 (20)

2. Primary Outcome

Title	PK: Area Under the Concentration Curve From Time 0 to Infinity [AUC (0-∞)] of Baricitinib
Time Frame	Days 1 and 5: predose of baricitinib, 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36, 48 and 72 (Day 5 dosing only) hours postdose

Outcome Measure Data

Analysis Population Description

All enrolled participants who received study drug (baricitinib in Period 1 and baricitinib + probenecid in Period 2) and had PK data to calculate AUC (0-∞) of baricitinib.

Arm/Group Title	Baricitinib	Baricitinib + Probenecid
Arm/Group Description	4 mg baricitinib tablet administered orally, once, on Day 1 in Period 1.	4 mg baricitinib tablet administered orally, once, on Day 5 in Period 2. 1000 mg probenecid tablet administered orally, BID, on Days 3 through 7 in Period 2.
Measure Participants	18	18
Geometric Mean (Geometric Coefficient of Variation) [nanograms*hour/milliliter (ng*h/mL)]	236 (22)	480 (14)

Adverse Events

Time Frame	Baseline through study completion (up to Day 18).
Arm/Group Title	Baricitinib		Probenecid		Baricitinib + Probenecid
Arm/Group Description	4 mg baricitinib tablet administered orally, once, on Day 1 in Period 1. Adverse events are reported from baseline through predose on Day 3.		1000 mg probenecid tablet administered orally, BID, on Days 3 through 4 in Period 2. Adverse events are reported from postdose on Day 3 through predose on Day 5.		4 mg baricitinib tablet administered orally, once, on Day 5 in Period 2. 1000 mg probenecid tablet administered orally, BID, on Days 5 through 7 in Period 2. Adverse events are reported from postdose on Day 5 up to Day 18.
All Cause Mortality
	Baricitinib		Probenecid		Baricitinib + Probenecid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Baricitinib		Probenecid		Baricitinib + Probenecid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Baricitinib		Probenecid		Baricitinib + Probenecid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/18 (16.7%)		3/18 (16.7%)		8/18 (44.4%)
Eye disorders
Ocular hyperaemia	0/18 (0%)	0	0/18 (0%)	0	1/18 (5.6%)	1
Gastrointestinal disorders
Abdominal pain upper	0/18 (0%)	0	1/18 (5.6%)	1	1/18 (5.6%)	1
Constipation	0/18 (0%)	0	1/18 (5.6%)	1	1/18 (5.6%)	1
General disorders
Catheter site pain	1/18 (5.6%)	1	0/18 (0%)	0	0/18 (0%)	0
Fatigue	2/18 (11.1%)	2	0/18 (0%)	0	0/18 (0%)	0
Influenza like illness	0/18 (0%)	0	0/18 (0%)	0	1/18 (5.6%)	1
Pain	0/18 (0%)	0	1/18 (5.6%)	1	0/18 (0%)	0
Infections and infestations
Oral herpes	0/18 (0%)	0	0/18 (0%)	0	1/18 (5.6%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	0/18 (0%)	0	1/18 (5.6%)	1	0/18 (0%)	0
Back pain	0/18 (0%)	0	0/18 (0%)	0	1/18 (5.6%)	1
Pain in extremity	1/18 (5.6%)	1	0/18 (0%)	0	0/18 (0%)	0
Nervous system disorders
Dizziness	0/18 (0%)	0	0/18 (0%)	0	1/18 (5.6%)	1
Headache	1/18 (5.6%)	1	1/18 (5.6%)	1	6/18 (33.3%)	6
Renal and urinary disorders
Urine odour abnormal	0/18 (0%)	0	1/18 (5.6%)	1	0/18 (0%)	0
Respiratory, thoracic and mediastinal disorders
Increased upper airway secretion	0/18 (0%)	0	1/18 (5.6%)	1	0/18 (0%)	0
Nasal congestion	1/18 (5.6%)	1	0/18 (0%)	0	0/18 (0%)	0
Skin and subcutaneous tissue disorders
Night sweats	0/18 (0%)	0	0/18 (0%)	0	1/18 (5.6%)	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.