A Study to Assess the Effect of Abiraterone Acetate in Male Participants With Mild or Moderate Hepatic Impairment Compared to Matched Control Participants With Normal Hepatic Function

A Phase 1 Single Dose Open-Label Pharmacokinetic Study of Abiraterone Acetate in Male Participants With Mild or Moderate Hepatic Impairment Compared to Matched Control Participants With Normal Hepatic Function

The purpose of this study is to evaluate the safety and pharmacokinetics (study of what the body does to a drug) of 1000 mg oral dose of abiraterone acetate and its major metabolite(s) with mild or moderate hepatic impairment and matched control Participants with normal hepatic function.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Abiraterone acetate

Detailed Description

This is an open-label (identity of assigned study drug will be known) pharmacokinetics and safety study of abiraterone acetate administered as four 250 mg tablets (1000 mg) to 3 cohorts (groups) in Cohort 1 (Mild Hepatic Impairment), Cohort 2 (Moderate Hepatic Impairment) and Cohort 3 (Normal Hepatic Function). There will be approximately 8 Participants per cohort (total of approximately 24 Participants for the study). The cohorts will be dosed sequentially and activities will consist of Screening, Study and Follow-up periods, a total of up to approximately 36 days. Possible Participants will be screened to assess their eligibility to enter the study within 14 days prior to study Day 1. Participants will be confined at the Clinical Research Center (CRC) from the time of Check-in on Day -1 until discharge on Day 5. Participants will return to the CRC on Days 8 and 15 and there will be a follow-up call or visit on Day 22. A review of all clinical and laboratory data through Day 8 evaluations in each cohort will be done by the Medical Monitor and the Principal Investigator (PI) prior to proceeding with dosing any further cohort, if indicated. Safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Non smokers or light smokers and willing to limit smoking for the period of confinement to 4 cigarettes per day
• Body Mass Index of 18-35 kg/m2
• Negative test for breathalyzer alcohol and drugs of abuse and HIV antibody test at Screening
• Agrees to protocol-defined use of effective contraception
• Participants with Mild or Moderate Hepatic Impairment
• Must have mild or moderate hepatic impairment
• On a stable dose of medication and/or treatment regimen for at least 2 weeks before dosing as well as during the study
• Clinical laboratory evaluations within the reference range for the test laboratory
• Participants with normal hepatic function have no clinically significant findings from medical history, physical examination, Laboratory values within protocol defined parameters

Exclusion Criteria:

• Any other investigational study drug trial within 5 half-lives of that investigational study drug or 30 days prior to dosing with Abiraterone acetate, whichever is longer
• Inability to swallow four (4) 250 mg abiraterone acetate tablets
• History of or current clinically significant medical illness that would potentially alter absorption and/or excretion of orally administered drugs
• History or presence of a clinically significant abnormal ECG
• Donation of blood or significant loss of blood within 56 days prior to Day 1 or planned donation of blood or plasma from Screening through 30 days after Day 1
• Use of any prescription medications/products or any OTC, non-prescription unrelated to existing allowable stable medical conditions within 5 half-lives of that product or 7 days prior to dosing with abiraterone acetate, whichever is longer
• Clinically significant renal laboratory findings
• Participants with Mild or Moderate Hepatic Impairment will be excluded - any significant medical history other than hepatic impairment that may affect the interpretation of the data or which otherwise contraindicates participation in the study
• 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 within 2 weeks
• Autoimmune liver disease; Esophageal variceal bleeding within 6 months prior to Screening, unless successfully treated with banding, Gastric varices
• Spontaneous bacterial peritonitis within 3 months prior to Screening
• Portosystemic shunt, Organ transplant, Wilson's disease, Cholestatic liver disease (e g , primary biliary cirrhosis or primary sclerosing cholangitis)
• Clinically significant laboratory findings except as related to hepatic impairment
• Control Participants with Normal Hepatic Function Any significant laboratory results, including specifically Positive for Hepatitis B or C, Hemoglobin < 12 0 g/dL LFTs outside of normal limits

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Mild Hepatic participants administered to four 250 mg tablets (1000 mg) orally on Day 1.	Drug: Abiraterone acetate; On the morning of Day 1, each participant was given four 250 mg tablets of abiraterone acetate with 240 mL of room temperature tap water. Dosing followed at least a 10-hour fast from food (not including water).
Experimental: Cohort 2; Moderate Hepatic participants administered to four 250 mg tablets (1000 mg) orally on Day 1.	Drug: Abiraterone acetate; On the morning of Day 1, each participant was given four 250 mg tablets of abiraterone acetate with 240 mL of room temperature tap water. Dosing followed at least a 10-hour fast from food (not including water).
Experimental: Cohort 3; Normal Hepatic participants administered to four 250 mg tablets (1000 mg) orally on Day 1.	Drug: Abiraterone acetate; On the morning of Day 1, each participant was given four 250 mg tablets of abiraterone acetate with 240 mL of room temperature tap water. Dosing followed at least a 10-hour fast from food (not including water).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum observed plasma concentration of abiraterone acetate	Up to 96 hours postdose

Secondary Outcome Measures

Outcome Measure	Time Frame
The number of Participants with adverse events	Approximately 36 days

Collaborators and Investigators

• Sponsor: Cougar Biotechnology, Inc.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): April 1, 2010

Study Registration Dates

• First Submitted: October 31, 2013
• First Submitted That Met QC Criteria: November 28, 2013
• First Posted (Estimate): December 5, 2013

Study Record Updates

• Last Update Posted (Estimate): December 5, 2013
• Last Update Submitted That Met QC Criteria: November 28, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Prostate Cancer; Abiraterone acetate
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Steroid Synthesis Inhibitors; Abiraterone Acetate
• Other Study ID Numbers: CR016948; COU-AA-011 (Other Identifier: Cougar Biotechnology, Inc.)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No