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

NCT00672581 | Completed Phase 1

• 2 other identifiers: D4320C000254054IL/0025
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatic Impairment

Keywords

Hepatic Impairment

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• 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

Study Arms (4)

1

EXPERIMENTAL

Control (healthy volunteers)

Drug: ZD4054

2

EXPERIMENTAL

Mild Hepatic Impairment

Drug: ZD4054

3

EXPERIMENTAL

Moderate Hepatic Impairment

Drug: ZD4054

4

EXPERIMENTAL

Severe Hepatic Impairment

Drug: ZD4054

Interventions

ZD4054 DRUG

10mg, Oral tablet, single dose

Also known as: Zibotentan

1; 2; 3; 4

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead
• PRA Health Sciences: collaborator

Study Sites (1)

Research Site

Prague, Czechia

Location

Related Publications (1)

• 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.

  PMID: 21414193 DERIVED

MeSH Terms

Interventions

ZD4054

Study Officials

• Thomas Morris

  AstraZeneca, Medical Science Director

  STUDY DIRECTOR

• Blanka Cieslarova, MD

  Medical Director & Head of Clinical Unit, PRA International

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 1, 2008
• First Posted: May 6, 2008
• Study Start: April 1, 2008
• Study Completion: March 1, 2009
• Last Updated: September 28, 2010

Record last verified: 2010-09

Locations

CZ (1)