Back to resultsPharmacokinetics, Safety & Tolerability of ZD4054 (Zibotentan) in Subjects With Normal, Mild, Moderate and Severe Hepatic Impairment
Primary Purpose
Hepatic Impairment
Status
Completed
Phase
Phase 1
Locations
Czech Republic
Study Type
Interventional
Intervention
ZD4054
Sponsored by
About this trial
This is an interventional treatment trial for Hepatic Impairment focused on measuring Hepatic Impairment
Eligibility Criteria
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
Sites / Locations
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
1
2
3
4
Arm Description
Control (healthy volunteers)
Mild Hepatic Impairment
Moderate Hepatic Impairment
Severe Hepatic Impairment
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Full Information
NCT ID
NCT00672581
First Posted
May 1, 2008
Last Updated
September 27, 2010
Sponsor
AstraZeneca
Collaborators
PRA Health Sciences
1. Study Identification
Unique Protocol Identification Number
NCT00672581
Brief Title
Pharmacokinetics, Safety & Tolerability of ZD4054 (Zibotentan) in Subjects With Normal, Mild, Moderate and Severe Hepatic Impairment
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 Type
Interventional
2. Study Status
Record Verification Date
September 2010
Overall Recruitment Status
Completed
Study Start Date
April 2008 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
AstraZeneca
Collaborators
PRA Health Sciences
4. Oversight
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatic Impairment
Keywords
Hepatic Impairment
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Control (healthy volunteers)
Arm Title
2
Arm Type
Experimental
Arm Description
Mild Hepatic Impairment
Arm Title
3
Arm Type
Experimental
Arm Description
Moderate Hepatic Impairment
Arm Title
4
Arm Type
Experimental
Arm Description
Severe Hepatic Impairment
Intervention Type
Drug
Intervention Name(s)
ZD4054
Other Intervention Name(s)
Zibotentan
Intervention Description
10mg, Oral tablet, single dose
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Morris
Organizational Affiliation
AstraZeneca, Medical Science Director
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Blanka Cieslarova, MD
Organizational Affiliation
Medical Director & Head of Clinical Unit, PRA International
Official's Role
Principal Investigator
Facility Information:
Facility Name
Research Site
City
Praha 4
Country
Czech Republic
Facility Name
Research Site
City
Praha 6
Country
Czech Republic
12. IPD Sharing Statement
Citations:
PubMed Identifier
21414193
Citation
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.
Results Reference
derived
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Pharmacokinetics, Safety & Tolerability of ZD4054 (Zibotentan) in Subjects With Normal, Mild, Moderate and Severe Hepatic Impairment
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