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

Phase 1

Completed

• Conditions: Hepatic Impairment
• Interventions: Drug: ZD4054

• Registration Number: NCT00672581
• Lead Sponsor: AstraZeneca

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 available

Study Timeline

• Study Start: 2008-04
• Study First Submitted: 2008-05-01
• Study First Submitted QC: 2008-05-01
• Study First Posted: 2008-05-06
• Study Completion: 2009-03
• Status Verified: 2010-09
• Last Update Submitted: 2010-09-27
• Last Update Posted: 2010-09-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	ZD4054	Control (healthy volunteers)
2	ZD4054	Mild Hepatic Impairment
3	ZD4054	Moderate Hepatic Impairment
4	ZD4054	Severe Hepatic Impairment

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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
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

Trial Locations

Locations (1)

Research Site; 🇨🇿 Praha 6, Czech Republic