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

This study has been completed.
Sponsor:
Collaborator:
PRA Health Sciences
Information provided by:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT00672581
First received: May 1, 2008
Last updated: September 27, 2010
Last verified: September 2010

May 1, 2008
September 27, 2010
April 2008
Not Provided
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 ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00672581 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Pharmacokinetics, Safety & Tolerability of ZD4054 (Zibotentan) in Subjects With Normal, Mild, Moderate and Severe Hepatic Impairment
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

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.

Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Hepatic Impairment
Drug: ZD4054
10mg, Oral tablet, single dose
Other Name: Zibotentan
  • 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
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.
 
Completed
32
March 2009
Not Provided

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
Both
18 Years to 75 Years
Yes
Contact information is only displayed when the study is recruiting subjects
Czech Republic
 
NCT00672581
D4320C00025, 4054IL/0025
No
Thomas Morris, Medical Science Director, ZD4054, AstraZeneca Pharmaceuticals
AstraZeneca
PRA Health Sciences
Study Director: Thomas Morris AstraZeneca, Medical Science Director
Principal Investigator: Blanka Cieslarova, MD Medical Director & Head of Clinical Unit, PRA International
AstraZeneca
September 2010

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