A Study of Baricitinib and Probenecid in Healthy Participants

A Study to Investigate the Potential Impact of Organic Anion Transporter 3 Inhibition by Probenecid on the Pharmacokinetics of Baricitinib (LY3009104) in Healthy Subjects

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).

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Baricitinib; Drug: Probenecid

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS2 9LH
      • 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.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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• Are participants who have previously completed or withdrawn from this study or any other study investigating baricitinib, and have previously received baricitinib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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: September 3, 2013
• First Submitted That Met QC Criteria: September 3, 2013
• First Posted (Estimate): September 9, 2013

Study Record Updates

• Last Update Posted (Actual): June 6, 2017
• Last Update Submitted That Met QC Criteria: May 15, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antirheumatic Agents; Gout Suppressants; Renal Agents; Uricosuric Agents; Probenecid
• Other Study ID Numbers: 14604; I4V-MC-JAGG (Other Identifier: Eli Lilly and Company)