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

Hepatic Impairment Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00672581
• Other study ID #: D4320C00025
• Secondary ID: 4054IL/0025
• Status: Completed
• Phase: Phase 1
• First received: May 1, 2008
• Last updated: September 27, 2010
• Start date: April 2008
• Est. completion date: March 2009

Study information

• Verified date: September 2010
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCzech Republic: State Institute for Drug Control
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: March 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatic Impairment
• Liver Diseases

Intervention

Drug:
• ZD4054
10mg, Oral tablet, single dose

Locations

Country	Name	City	State
Czech Republic	Research Site	Praha 4
Czech Republic	Research Site	Praha 6

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	PRA Health Sciences

Country where clinical trial is conducted

Czech Republic, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	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	No