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

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

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.


Condition Intervention Phase
Hepatic Impairment
Drug: ZD4054
Phase 1

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

Further study details as provided by AstraZeneca:

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. [ 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 ]

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. [ 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 ]

Estimated Enrollment: 32
Study Start Date: April 2008
Study Completion Date: March 2009
Arms Assigned Interventions
Experimental: 1
Control (healthy volunteers)
Drug: ZD4054
10mg, Oral tablet, single dose
Other Name: Zibotentan
Experimental: 2
Mild Hepatic Impairment
Drug: ZD4054
10mg, Oral tablet, single dose
Other Name: Zibotentan
Experimental: 3
Moderate Hepatic Impairment
Drug: ZD4054
10mg, Oral tablet, single dose
Other Name: Zibotentan
Experimental: 4
Severe Hepatic Impairment
Drug: ZD4054
10mg, Oral tablet, single dose
Other Name: Zibotentan

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00672581

Locations
Czech Republic
Research Site
Praha 4, Czech Republic
Research Site
Praha 6, Czech Republic
Sponsors and Collaborators
AstraZeneca
PRA International
Investigators
Study Director: Thomas Morris AstraZeneca, Medical Science Director
Principal Investigator: Blanka Cieslarova, MD Medical Director & Head of Clinical Unit, PRA International
  More Information

No publications provided by AstraZeneca

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Thomas Morris, Medical Science Director, ZD4054, AstraZeneca Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00672581     History of Changes
Other Study ID Numbers: D4320C00025, 4054IL/0025
Study First Received: May 1, 2008
Last Updated: September 27, 2010
Health Authority: United States: Food and Drug Administration
Czech Republic: State Institute for Drug Control

Keywords provided by AstraZeneca:
Hepatic Impairment

Additional relevant MeSH terms:
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on September 29, 2014