Clinical trial NCT01767948: A Study to Evaluate the Pharmacokinetics of PCI-32765 in Participants With Varying Degrees of Hepatic Impairment
Official title: An Open-Label, Multicenter, Pharmacokinetic Study of PCI-32765 in Subjects With Varying Degrees of Hepatic Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatic Impairment
Keywords: Hepatic Impairment
PCI 32765
Metabolite PCI-45227
Pharmacokinetics
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2013-01-15
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum plasma concentration of PCI-32765
timeFrame: 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
measure: Area under the plasma concentration of PCI-32765
timeFrame: 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 outcomes:
measure: Number of participants with adverse events
timeFrame: up to Day 5
Other outcomes:
Locations:
city: Costa Mesa
country: United States
state: California
city: Orlando
country: United States
state: Florida
city: Knoxville
country: United States
state: Tennessee
city: San Antonio
country: United States
state: Texas
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical trial
role: STUDY_DIRECTOR
References:
citation: 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.