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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01516047
First received: January 19, 2012
Last updated: June 24, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Hepatic Impairment
Drug: Cohort 1
Drug: Cohort 2
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Pharmacokinetic Study of Abiraterone Acetate Suspension in Subjects With Severe Hepatic Impairment Compared to Matched Control Subjects With Normal Hepatic Function

Resource links provided by NLM:


Further study details as provided by Janssen Research & Development, LLC:

Primary Outcome Measures:
  • Mean plasma concentrations of abiraterone [ Time Frame: Up to Day 4 ] [ Designated as safety issue: No ]
  • Mean plasma protein binding concentrations of abiraterone [ Time Frame: Screening Day -2 ] [ Designated as safety issue: No ]
  • Maximum plasma concentrations of abiraterone [ Time Frame: Up to Day 4 ] [ Designated as safety issue: No ]
  • Time to reach the maximum plasma concentration of abiraterone [ Time Frame: Up to Day 4 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time 0 to 24 hours after dosing of abiraterone [ Time Frame: Up to Day 4 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration of abiraterone [ Time Frame: Up to Day 4 ] [ Designated as safety issue: No ]
  • Area under the plasma concentration-time curve from time 0 to infinite time of abiraterone [ Time Frame: Up to Day 4 ] [ Designated as safety issue: No ]
  • Percentage of area under the plasma concentration-time curve from time 0 to infinite time obtained by extrapolation of abiraterone [ Time Frame: Up to Day 4 ] [ Designated as safety issue: No ]
  • Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve of abiraterone [ Time Frame: Up to Day 4 ] [ Designated as safety issue: No ]
  • Time to last quantifiable plasma concentration of abiraterone [ Time Frame: Up to Day 4 ] [ Designated as safety issue: No ]
  • Total apparent clearance of drug after extravascular administration uncorrected for absolute bioavailability of abiraterone [ Time Frame: Up to Day 4 ] [ Designated as safety issue: No ]
  • Apparent volume of distribution after extravascular administration uncorrected for absolute bioavailability of abiraterone [ Time Frame: Up to Day 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The number of participants affected by an adverse event [ Time Frame: Up to Day 29 ] [ Designated as safety issue: Yes ]

Enrollment: 16
Study Start Date: January 2012
Study Completion Date: September 2012
Primary Completion Date: September 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Patients with severe hepatic impairment.
Drug: Cohort 1
125 mg to 2000 mg abiraterone acetate suspension on Day 1
Experimental: Cohort 2
Healthy individuals with normal hepatic function.
Drug: Cohort 2
2000 mg abiraterone acetate suspension on Day 1

Detailed Description:

This is a non-randomized (individuals will not be assigned by chance to study treatments), open-label (individuals will know the identity of study treatments), single dose, 2-cohort study of abiraterone acetate in approximately 16 adult men. Participants will either have severe hepatic impairment (Cohort 1) or qualify for the control group with normal hepatic function (Cohort 2). This study will consist of a screening period followed by a 4-day open-label treatment phase and subsequently a 28-day follow up after the study dose of abiraterone acetate suspension. Patients will be admitted to the study center on Day -1, a single dose of study drug will be administered on the morning of Day 1, and patients will remain at the study center until completion of the 72-hour pharmacokinetic (PK; study of what the body does to a drug) blood sample collection in the morning of Day 4. Enrollment will begin sequentially with patients in the severe hepatic impairment cohort. Enrollment for Cohort 1 will be staggered in order to evaluate safety and tolerability. The study will not proceed if >=Grade 3 toxicity or serious adverse events considered related to abiraterone acetate are observed. Additional patients may be enrolled if at least 8 patients in each cohort do not complete the required assessments, including the PK blood sample collections. The aim will be to treat the remaining patients in Cohort 1 at a suspension dose yielding an exposure equivalent to 1000 mg tablet in healthy individuals. If the dose is adjusted after Study Evaluation Team review, additional patients may be enrolled to ensure at least 8 patients complete the study at the final dose. Once enrollment of patients in the severe hepatic impairment cohort is completed, the matched-control cohort will be dosed. Serial PK samples will be collected during the open-label treatment phase as detailed in the protocol. Safety will be monitored throughout the study.

  Eligibility

Ages Eligible for Study:   35 Years to 80 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01516047

Locations
United States, California
Anaheim, California, United States
United States, Florida
Orlando, Florida, United States
United States, Texas
San Antonio, Texas, United States
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Study Director: Janssen Research & Development, LLC Clinical Research Janssen Research & Development, LLC
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01516047     History of Changes
Other Study ID Numbers: CR100779, 212082PCR1004
Study First Received: January 19, 2012
Last Updated: June 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Janssen Research & Development, LLC:
Hepatic impairment
Pharmacology
Pharmacokinetics
Pharmacodynamics
Abiraterone acetate suspension
JNJ-212082

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on August 28, 2014