A Pharmacokinetic Study of Abiraterone Acetate in Patients With Severe Hepatic Impairment Compared to Patients With Normal Hepatic Function

NCT01516047 | Completed Phase 1 DMC

• 2 other identifiers: CR100779212082PCR1004
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to evaluate systemic exposure of abiraterone acetate in adult male patients with severe hepatic impairment and is being conducted to collect information that will support clinical dosing recommendations for this subpopulation.

Conditions

Hepatic Impairment

Keywords

Hepatic impairment; Pharmacology; Pharmacokinetics; Pharmacodynamics; Abiraterone acetate suspension; JNJ-212082

Outcome Measures

Primary Outcomes (12)

• Mean plasma concentrations of abiraterone

  Up to Day 4

• Mean plasma protein binding concentrations of abiraterone

  Screening Day -2

• Maximum plasma concentrations of abiraterone

  Up to Day 4

• Time to reach the maximum plasma concentration of abiraterone

  Up to Day 4

• Area under the plasma concentration-time curve from time 0 to 24 hours after dosing of abiraterone

  Up to Day 4

• Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration of abiraterone

  Up to Day 4

• Area under the plasma concentration-time curve from time 0 to infinite time of abiraterone

  Up to Day 4

• Percentage of area under the plasma concentration-time curve from time 0 to infinite time obtained by extrapolation of abiraterone

  Up to Day 4

• Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve of abiraterone

  Up to Day 4

• Time to last quantifiable plasma concentration of abiraterone

  Up to Day 4

• Total apparent clearance of drug after extravascular administration uncorrected for absolute bioavailability of abiraterone

  Up to Day 4

• Apparent volume of distribution after extravascular administration uncorrected for absolute bioavailability of abiraterone

  Up to Day 4

Secondary Outcomes (1)

• The number of participants affected by an adverse event

  Up to Day 29

Study Arms (2)

Cohort 1

EXPERIMENTAL

Patients with severe hepatic impairment.

Drug: Cohort 1

Cohort 2

EXPERIMENTAL

Healthy individuals with normal hepatic function.

Drug: Cohort 2

Interventions

Cohort 1 DRUG

125 mg to 2000 mg abiraterone acetate suspension on Day 1

Cohort 1

Cohort 2 DRUG

2000 mg abiraterone acetate suspension on Day 1

Cohort 2

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants are to be cancer free and have a body mass index (BMI) between 18 kg/m2 to 40 kg/m2, inclusive, and body weight not less than 50 kg.
• Cohort 1is characterized by severe hepatic impairment (as described by the Child-Pugh Classification C).
• Cohort 2 represents a matched control characterized by healthy participants with normal hepatic function.
• Control cohort participants will be age matched ± 10 years and BMI matched within 20% of the means of the severe hepatic impairment cohort; no other clinical criteria will be matched.
• Control cohort participants must be in good health, with no clinically significant findings from medical history, physical examination, laboratory evaluations, 12-lead electrocardiogram and vital signs.
• Patients with hepatic impairment are required to be on medication and/or treatment regimen to treat their underlying hepatic impairment or medical conditions before dosing with study drug.

You may not qualify if:

• Participants in the control cohort who test positive for hepatitis B surface antigen (HBsAg) or hepatitis C antibodies will not be permitted to enroll in the study.
• Patients with hepatic impairment who have acute or exacerbating hepatitis, fluctuating or rapidly deteriorating hepatic function as indicated by widely varying or worsening of clinical and/or laboratory signs of hepatic impairment in the judgment of either the investigator or the sponsor's medical monitor will be excluded from participating in the study.
• Patients with hepatic impairment taking antiviral therapy for treatment of active hepatitis infection at the time of screening, previously diagnosed with hepatocellular carcinoma, or who have a history of biliary sepsis within the past 2 years.
• Patients with severe hepatic impairment should not have Gilbert's syndrome or \>= Grade 3 hepatic encephalopathy where the patient lacks the capacity to provide informed consent as judged by the investigator. Mild or moderate hepatic encephalopathy that would not impede informed consent in the investigator's judgment is permitted.

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (3)

Unknown Facility

Anaheim, California, United States

Location

Unknown Facility

Orlando, Florida, United States

Location

Unknown Facility

San Antonio, Texas, United States

Location

Related Publications (1)

• Marbury T, Lawitz E, Stonerock R, Gonzalez M, Jiao J, Breeding J, Haqq C, Verboven P, Stieltjes H, Yu M, Molina A, Acharya M, Chien C, Tran N. Single-dose pharmacokinetic studies of abiraterone acetate in men with hepatic or renal impairment. J Clin Pharmacol. 2014 Jul;54(7):732-41. doi: 10.1002/jcph.253. Epub 2014 Jan 17.

  PMID: 24374856 DERIVED

Related Links

• An Open-Label Pharmacokinetic Study of Abiraterone Acetate Suspension in Subjects with Severe Hepatic Impairment Compared to Matched Control Subjects with Normal Hepatic Function

MeSH Terms

Interventions

KPNA1 protein, human

Study Officials

• Janssen Research & Development, LLC Clinical Research

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2012
• First Posted: January 24, 2012
• Study Start: January 1, 2012
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: June 25, 2014

Record last verified: 2014-06

Locations

US (3)