A Study to Evaluate the Pharmacokinetics of PCI-32765 in Participants With Varying Degrees of Hepatic Impairment

Phase 1

Completed

• Conditions: Hepatic Impairment
• Interventions: Drug: PCI-32765

• Registration Number: NCT01767948
• Lead Sponsor: Janssen Research & Development, LLC

Brief Summary

The purpose of this study is to evaluate the pharmacokinetics (how the drug concentrations change over time) of PCI 32765 in participants with mild, moderate, or severe hepatic impairment.

Detailed Description

This is an open-label (all people know the identity of the intervention), single-dose, multi-center (study conducted at multiple sites), non-randomized study to access the pharmacokinetics of PCI-32765 in participants who either have mild, moderate, or severe hepatic impairment or qualify for the control group (normal liver function). The study mainly consists of 3 phases: screening phase (within 21 days prior to the first dose of study medication), treatment phase, and a follow up phase (10 to 12 days after the last dose of study medication). In the treatment phase, participants will receive single oral dose of PCI-32765 on Day 1. Liver impairment will be classified according to the Child-Pugh Classification of Severity of Liver Disease, as: normal, mild, moderate, and severe. Total 30 participants (24 with hepatic impairment \[6 mild, 9 moderate and 9 severe\] at baseline and 6 in the control group according to Child-Pugh criteria) will be enrolled. Participants in the control group will be enrolled after the participants with mild or moderate hepatic impairment have completed the study. Safety evaluations for adverse events, clinical laboratory tests, electrocardiogram, vital signs, and physical examination will be monitored throughout the study. The total duration of study for each participant will be approximately for 29 to 33 days.

Study Timeline

• Study Start: 2012-12
• Study First Submitted: 2013-01-09
• Study First Submitted QC: 2013-01-11
• Study First Posted: 2013-01-15
• Primary Completion: 2013-11
• Study Completion: 2013-11
• Status Verified: 2014-10
• Last Update Submitted: 2014-10-06
• Last Update Posted: 2014-10-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Stable hepatic function as confirmed by the serum bilirubin and transaminase levels measured during screening and those measured within 48 hours prior to PCI-32765 administration
• Must be hepatically impaired as defined by the Child-Pugh classification of severity of liver disease
• Control group must have good health with normal liver function
• Participants with controlled hypertension and those with problems directly associated with the primary diagnosis of hepatic impairment
• Concomitant medications to treat underlying disease states or medical conditions related to hepatic impairment are allowed
• Agrees to protocol-defined use of effective contraception

Exclusion Criteria

• Clinically significant renal laboratory findings including serum creatinine more than 1.5 x the upper limit of normal (ULN) and/or calculated creatinine clearance of less than 60 ml per minute per 1.73 square meter
• Clinically significant abnormal laboratory tests, physical examination, vital signs or electrocardiogram at screening or at admission to the study center
• Antiviral therapy for active hepatitis infection at time of screening
• Use of any anti-coagulation therapy including vitamin K antagonists, low molecular weight heparin, or other anticoagulants

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients with severe hepatic function	PCI-32765	Patients will receive PCI-32765 140 mg, orally, as a single dose, on Day 1.
Patients with moderate hepatic function	PCI-32765	Patients will receive PCI-32765 140 mg, orally, as a single dose, on Day 1.
Patients with mild hepatic function	PCI-32765	Patients will receive PCI-32765 140 mg, orally, as a single dose, on Day 1.
Patients with normal hepatic function	PCI-32765	Patients will receive PCI-32765 140 mg, orally, as a single dose, on Day 1.

Primary Outcome Measures

Name	Time	Method
Maximum plasma concentration of PCI-32765	Predose, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours, and 96 hours
Area under the plasma concentration of PCI-32765	Predose, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours, and 96 hours

Secondary Outcome Measures

Name	Time	Method
Number of participants with adverse events	up to Day 5