Back to resultsA Pharmacokinetic Study of Abiraterone Acetate in Patients With Severe Hepatic Impairment Compared to Patients With Normal Hepatic Function
Primary Purpose
Hepatic Impairment
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Cohort 1
Cohort 2
Sponsored by
About this trial
This is an interventional treatment trial for Hepatic Impairment focused on measuring Hepatic impairment, Pharmacology, Pharmacokinetics, Pharmacodynamics, Abiraterone acetate suspension, JNJ-212082
Eligibility 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Arm Description
Patients with severe hepatic impairment.
Healthy individuals with normal hepatic function.
Outcomes
Primary Outcome Measures
Mean plasma concentrations of abiraterone
Mean plasma protein binding concentrations of abiraterone
Maximum plasma concentrations of abiraterone
Time to reach the maximum plasma concentration of abiraterone
Area under the plasma concentration-time curve from time 0 to 24 hours after dosing of abiraterone
Area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration of abiraterone
Area under the plasma concentration-time curve from time 0 to infinite time of abiraterone
Percentage of area under the plasma concentration-time curve from time 0 to infinite time obtained by extrapolation of abiraterone
Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve of abiraterone
Time to last quantifiable plasma concentration of abiraterone
Total apparent clearance of drug after extravascular administration uncorrected for absolute bioavailability of abiraterone
Apparent volume of distribution after extravascular administration uncorrected for absolute bioavailability of abiraterone
Secondary Outcome Measures
The number of participants affected by an adverse event
Full Information
NCT ID
NCT01516047
First Posted
January 19, 2012
Last Updated
June 24, 2014
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT01516047
Brief Title
A Pharmacokinetic Study of Abiraterone Acetate in Patients With Severe Hepatic Impairment Compared to Patients With Normal Hepatic Function
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
Study Type
Interventional
2. Study Status
Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
January 2012 (undefined)
Primary Completion Date
September 2012 (Actual)
Study Completion Date
September 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment
Keywords
Hepatic impairment, Pharmacology, Pharmacokinetics, Pharmacodynamics, Abiraterone acetate suspension, JNJ-212082
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Patients with severe hepatic impairment.
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Healthy individuals with normal hepatic function.
Intervention Type
Drug
Intervention Name(s)
Cohort 1
Intervention Description
125 mg to 2000 mg abiraterone acetate suspension on Day 1
Intervention Type
Drug
Intervention Name(s)
Cohort 2
Intervention Description
2000 mg abiraterone acetate suspension on Day 1
Primary Outcome Measure Information:
Title
Mean plasma concentrations of abiraterone
Time Frame
Up to Day 4
Title
Mean plasma protein binding concentrations of abiraterone
Time Frame
Screening Day -2
Title
Maximum plasma concentrations of abiraterone
Time Frame
Up to Day 4
Title
Time to reach the maximum plasma concentration of abiraterone
Time Frame
Up to Day 4
Title
Area under the plasma concentration-time curve from time 0 to 24 hours after dosing of abiraterone
Time Frame
Up to Day 4
Title
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
Title
Area under the plasma concentration-time curve from time 0 to infinite time of abiraterone
Time Frame
Up to Day 4
Title
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
Title
Elimination half-life associated with the terminal slope of the semilogarithmic drug concentration-time curve of abiraterone
Time Frame
Up to Day 4
Title
Time to last quantifiable plasma concentration of abiraterone
Time Frame
Up to Day 4
Title
Total apparent clearance of drug after extravascular administration uncorrected for absolute bioavailability of abiraterone
Time Frame
Up to Day 4
Title
Apparent volume of distribution after extravascular administration uncorrected for absolute bioavailability of abiraterone
Time Frame
Up to Day 4
Secondary Outcome Measure Information:
Title
The number of participants affected by an adverse event
Time Frame
Up to Day 29
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Research
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Anaheim
State/Province
California
Country
United States
City
Orlando
State/Province
Florida
Country
United States
City
San Antonio
State/Province
Texas
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
24374856
Citation
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.
Results Reference
derived
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_JNJ_6051&studyid=3447&filename=CR100779_CSR.pdf
Description
An Open-Label Pharmacokinetic Study of Abiraterone Acetate Suspension in Subjects with Severe Hepatic Impairment Compared to Matched Control Subjects with Normal Hepatic Function
Learn more about this trial
A Pharmacokinetic Study of Abiraterone Acetate in Patients With Severe Hepatic Impairment Compared to Patients With Normal Hepatic Function
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