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

An Open-Label, Multicenter, Pharmacokinetic Study of PCI-32765 in Subjects With Varying Degrees of Hepatic Impairment

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: PCI-32765

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Costa Mesa, California, 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 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Patients with mild hepatic function; Patients will receive PCI-32765 140 mg, orally, as a single dose, on Day 1.	Drug: PCI-32765; PCI-32765 140 mg will be administered as a single dose, orally, on Day 1.
EXPERIMENTAL: Patients with moderate hepatic function; Patients will receive PCI-32765 140 mg, orally, as a single dose, on Day 1.	Drug: PCI-32765; PCI-32765 140 mg will be administered as a single dose, orally, on Day 1.
EXPERIMENTAL: Patients with severe hepatic function; Patients will receive PCI-32765 140 mg, orally, as a single dose, on Day 1.	Drug: PCI-32765; PCI-32765 140 mg will be administered as a single dose, orally, on Day 1.
EXPERIMENTAL: Patients with normal hepatic function; Patients will receive PCI-32765 140 mg, orally, as a single dose, on Day 1.	Drug: PCI-32765; PCI-32765 140 mg will be administered as a single dose, orally, on Day 1.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
Number of participants with adverse events	up to Day 5

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• de Jong J, Skee D, Hellemans P, Jiao J, de Vries R, Swerts D, Lawitz E, Marbury T, Smith W, Sukbuntherng J, Mannaert E. Single-dose pharmacokinetics of ibrutinib in subjects with varying degrees of hepatic impairment<sup/> Leuk Lymphoma. 2017 Jan;58(1):185-194. doi: 10.1080/10428194.2016.1189548. Epub 2016 Jun 7.

Helpful Links

• An Open-Label, Multicenter, Pharmacokinetic Study of PCI-32765 in Subjects with Varying Degrees of Hepatic Impairment(18343).

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (ACTUAL): November 1, 2013
• Study Completion (ACTUAL): November 1, 2013

Study Registration Dates

• First Submitted: January 9, 2013
• First Submitted That Met QC Criteria: January 11, 2013
• First Posted (ESTIMATE): January 15, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): October 7, 2014
• Last Update Submitted That Met QC Criteria: October 6, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Hepatic Impairment; PCI 32765; Metabolite PCI-45227
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases
• Other Study ID Numbers: CR100944; PCI-32765CLL1006 (OTHER: Janssen Research & Development, LLC)