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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00672581
Recruitment Status : Completed
First Posted : May 6, 2008
Last Update Posted : September 28, 2010
Sponsor:
Collaborator:
PRA Health Sciences
Information provided by:
AstraZeneca

Tracking Information
First Submitted Date  ICMJE May 1, 2008
First Posted Date  ICMJE May 6, 2008
Last Update Posted Date September 28, 2010
Study Start Date  ICMJE April 2008
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: September 27, 2010)
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. [ Time Frame: predose and 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post-dose ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 1, 2008)
To characterise the pharmacokinetic profile of ZD4054 following a single 10 mg oral dose in subjects with normal hepatic function and in subjects with varying degrees of hepatic impairment. [ Time Frame: predose and 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72, 96, 120 hours post-dose ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2010)
  • 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. [ Time Frame: Predose until post-study medical ]
  • 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. [ Time Frame: 3 hour post-dose ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2008)
  • To assess the safety of ZD4054 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. [ Time Frame: Predose until post-study medical ]
  • To explore changes in protein binding of ZD4054 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. [ Time Frame: 3 hour post-dose ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pharmacokinetics, Safety & Tolerability of ZD4054 (Zibotentan) in Subjects With Normal, Mild, Moderate and Severe Hepatic Impairment
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hepatic Impairment
Intervention  ICMJE Drug: ZD4054
10mg, Oral tablet, single dose
Other Name: Zibotentan
Study Arms  ICMJE
  • Experimental: 1
    Control (healthy volunteers)
    Intervention: Drug: ZD4054
  • Experimental: 2
    Mild Hepatic Impairment
    Intervention: Drug: ZD4054
  • Experimental: 3
    Moderate Hepatic Impairment
    Intervention: Drug: ZD4054
  • Experimental: 4
    Severe Hepatic Impairment
    Intervention: Drug: ZD4054
Publications * Tomkinson H, Kemp J, Oliver S, Swaisland H, Taboada M, Morris T. Pharmacokinetics and tolerability of zibotentan (ZD4054) in subjects with hepatic or renal impairment: two open-label comparative studies. BMC Clin Pharmacol. 2011 Mar 17;11:3. doi: 10.1186/1472-6904-11-3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Estimated Enrollment  ICMJE
 (submitted: May 1, 2008)
32
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2009
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Czech Republic
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00672581
Other Study ID Numbers  ICMJE D4320C00025
4054IL/0025
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Thomas Morris, Medical Science Director, ZD4054, AstraZeneca Pharmaceuticals
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE PRA Health Sciences
Investigators  ICMJE
Study Director: Thomas Morris AstraZeneca, Medical Science Director
Principal Investigator: Blanka Cieslarova, MD Medical Director & Head of Clinical Unit, PRA International
PRS Account AstraZeneca
Verification Date September 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP