A Study to Evaluate the Pharmacokinetics of JNJ-38518168 in Patients With Mild and Moderate Hepatic Impairment Compared With Patients With Normal Hepatic Function

An Open-Label Study to Evaluate the Pharmacokinetics of Multiple Oral Doses of 30 mg JNJ-38518168 in Subjects With Mild and Moderate Hepatic Impairment Compared With Subjects With Normal Hepatic Function

The purpose of this study is to characterize the pharmacokinetics (what the body does to the study medication) of JNJ-38518168 at approximately steady-state (stable medication levels) after administration of multiple oral 30 mg doses of JNJ-38518168 to participants with mild or moderate hepatic (liver) impairment (abnormal function) compared with participants with normal hepatic function.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: JNJ-38518168

Detailed Description

This is an open-label (both [participants and investigator] know what treatment participants will receive) and multicenter study. The study consists of 3 phases: a screening phase (approximately 3 weeks), a treatment phase (from day -2 [2 days before the administration of study medication] to Day 18), and an end-of-study phase (7 to 10 days after the last dose of study medication). Approximately 24 participants (participants with mild hepatic impairment, moderate hepatic impairment, and normal liver function) will receive JNJ-38518168 for 14 days. Hepatic impairment will be evaluated according to Child-Pugh score. It consists of 5 clinical measures (amount of ascites [an abnormal accumulation of fluid in the abdomen], total bilirubin [mg/dL], albumin [g/dL], international normalized ratio, and degree of encephalopathy [abnormal functioning of the brain]). Each is scored from 0 (less severity) to 3 (highest severity). Total Child-Pugh score is the sum of all subscores and is graded as: mild (5-6 points), moderate (7-9 points), and severe (10-15 points). Safety will be evaluated by the assessment of adverse events, clinical laboratory tests, vital signs, body weight, physical examination, and 12-lead electrocardiogram which will be monitored at various timepoints throughout the study. The total duration of study participation for each participant is approximately 6 weeks.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States
  • Tennessee
    • Knoxville, Tennessee, United States
  • Texas
    • San Antonio, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Have normal liver function for the normal hepatic function group
• Have mild or moderate liver diseases as defined by the Child-Pugh Classification and be clinically stable overall for the mild or moderate liver disease groups
• Doses of drugs used to treat other illnesses or conditions related to liver disease must be stable for at least 4 weeks before the first dose of study medication with the exception of thyroid replacement hormone, in which case the dose must be stable for 3 months before the first dose of study medication. Doses of these drugs must also be stable during the course of the study
• If an illness with a fever occurs within one week of the start of dosing, dosing must be postponed until the body temperature is normal for at least 72 hours
• Participants must agree to use one of the contraception methods defined in the protocol

Exclusion criteria:

• Hepatic insufficiency secondary to autoimmune hepatitis or obstructive liver disease
• Allergy to heparin or history of heparin-induced thrombocytopenia
• All participants must have a negative human immunodeficiency virus test. Participants with normal liver function must test negative for hepatitis B and hepatitis C
• Severe ascites (an abnormal accumulation of fluid in the abdomen) or severe pleural effusion (fluid around the lungs)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JNJ-38518168	Drug: JNJ-38518168; All participants will receive JNJ-38518168 30 mg tablet once daily from Day 1 to Day 14.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed plasma concentration of JNJ-38518168 at approximately steady-state after multiple doses	Day 14 (predose, postdose [1, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, and 96 hours])
Area under the plasma concentration-time curve of JNJ-38518168 at approximately steady-state after multiple doses	Day 14 (predose, postdose [1, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, and 96 hours])
Time to reach the maximum observed plasma of JNJ-38518168 at approximately steady-state after multiple doses	Day 14 (predose, postdose [1, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, and 96 hours])
Apparent clearance of JNJ-38518168 at approximately steady-state after multiple doses	Day 14 (predose, postdose [1, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48, 72, and 96 hours])

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum observed plasma concentration of JNJ-38518168 after single dose	Day 1 (predose, postdose [1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours])
Area under the plasma concentration-time curve of JNJ-38518168 after single dose	Day 1 (predose, postdose [1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours])
Time to reach the maximum observed plasma of JNJ-38518168 after single dose	Day 1 (predose, postdose [1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours])
Urine concentration-time data of JNJ-38518168 after single dose	Day 1 (predose, postdose [1, 2, 3, 4, 5, 6, 7, 8, 12, and 24 hours])
Plasma protein binding of JNJ-38518168	Day 1 (postdose [4 hours]) and Day 14 (predose, postdose [4 hours])
Number of participants with adverse events	Up to 6 weeks

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: May 23, 2013
• First Submitted That Met QC Criteria: May 23, 2013
• First Posted (Estimate): May 29, 2013

Study Record Updates

• Last Update Posted (Estimate): May 12, 2016
• Last Update Submitted That Met QC Criteria: May 10, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Hepatic Impairment; JNJ-38518168; Mild and moderate hepatic impairment; Normal hepatic function
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: CR101336; 38518168ARA1005 (Other Identifier: Janssen Research & Development, LLC)