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Pharmacokinetics, Safety & Tolerability of ZD4054 (Zibotentan) in Subjects With Normal, Mild, Moderate and Severe Hepatic Impairment

Sponsor
AstraZeneca (Industry)
Overall Status
Completed
CT.gov ID
NCT00672581
Collaborator
PRA Health Sciences (Industry)
32
Enrollment
2
Locations
4
Arms
11
Duration (Months)
16
Patients Per Site
1.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to compare how ZD4054 (Zibotentan) is taken up, how it is broken down and removed from the body in subjects with liver cirrhosis and hepatic impairment compared to healthy subjects of a similar age, sex and weight. As for all clinical trials, safety and tolerability of the drug will be evaluated as well to develop dosing recommendations for dosing of ZD4054 (Zibotentan) in subjects with varying stages of hepatic impairment.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
32 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-label Comparative Study of the Pharmacokinetics, Safety and Tolerability of ZD4054 (Zibotentan) Following a 10 mg Single Oral Dose of ZD4054(Zibotentan) to Healthy Subjects and to Subjects With Mild, Moderate and Severe Hepatic Impairment
Study Start Date :
Apr 1, 2008
Actual Study Completion Date :
Mar 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1

Control (healthy volunteers)

Drug: ZD4054
10mg, Oral tablet, single dose
Other Names:
  • Zibotentan

    		•
    Experimental: 2

    Mild Hepatic Impairment

    Drug: ZD4054
    10mg, Oral tablet, single dose
    Other Names:
  • Zibotentan

    		•
    Experimental: 3

    Moderate Hepatic Impairment

    Drug: ZD4054
    10mg, Oral tablet, single dose
    Other Names:
  • Zibotentan

    		•
    Experimental: 4

    Severe Hepatic Impairment

    Drug: ZD4054
    10mg, Oral tablet, single dose
    Other Names:
  • Zibotentan

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Characterise the pharmacokinetic profile of ZD4054 (Zibotentan) following a single 10 mg oral dose in subjects with normal hepatic function and in subjects with varying degrees of hepatic impairment. [predose and 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post-dose]

    Secondary Outcome Measures

    1. Assess the safety of Zibotentan following a single 10 mg oral dose in subjects with normal hepatic function and in subjects with varying degrees of hepatic impairment by assessment of vital signs, ECG, clinical chemistry, haematology and adverse events. [Predose until post-study medical]

    2. Explore changes in protein binding of Zibotentan and the subsequent effects on its pharmacokinetics in subjects with normal hepatic function and in subjects with varying degrees of hepatic impairment by assessment of free Cmax, free AUC and unbound CL/F. [3 hour post-dose]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:

    • Hepatically impaired subjects - Subjects with stable liver cirrhosis and hepatic impairment for at least 3 months prior to the start of the study.

    • Healthy volunteers - Clinical laboratory tests within the normal reference range or results with minor deviations which are not considered by the Investigator to be clinically significant

    Exclusion Criteria:

    • In the opinion of the investigator, any evidence of additional severe or uncontrolled systemic disease (eg, cardiac, or renal disease) or evidence of any other significant clinical disorder or laboratory finding

    • Healthy volunteers - History or presence of hepatic disease known to interfere with absorption, distribution, metabolism or excretion of drug

    • Hepatically impaired subjects - Fluctuating or rapidly deteriorating hepatic function as indicated by widely varying or worsening of clinical and/or laboratory signs of hepatic impairment within the screening period

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Praha 4 Czech Republic
    2 Research Site Praha 6 Czech Republic

    Sponsors and Collaborators

    • AstraZeneca
    • PRA Health Sciences

    Investigators

    • Study Director: Thomas Morris, AstraZeneca, Medical Science Director
    • Principal Investigator: Blanka Cieslarova, MD, Medical Director & Head of Clinical Unit, PRA International

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    , ,
    ClinicalTrials.gov Identifier:
    NCT00672581
    Other Study ID Numbers:
    • D4320C00025
    • 4054IL/0025
    First Posted:
    May 6, 2008
    Last Update Posted:
    Sep 28, 2010
    Last Verified:
    Sep 1, 2010
    Keywords provided by , ,
    Hepatic Impairment
    Additional relevant MeSH terms:
    Liver Diseases

    Study Results

    No Results Posted as of Sep 28, 2010