Pharmacokinetics, Safety & Tolerability of ZD4054 in Subjects With Normal, Mild, Moderate and Severe Hepatic Impairment - Full Text View

Sponsors and Collaborators:	AstraZeneca PRA International
Information provided by:	AstraZeneca
ClinicalTrials.gov Identifier:	NCT00672581

Purpose

This study is designed to compare how ZD4054 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 in subjects with varying stages of hepatic impairment.

Condition	Intervention	Phase
Hepatic Impairment	Drug: ZD4054	Phase I

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Parallel Assignment, Pharmacokinetics Study
Official Title:	An Open-Label Comparative Study of the Pharmacokinetics, Safety and Tolerability of ZD4054 Following a 10 mg Single Oral Dose of ZD4054 to Healthy Subjects and to Subjects With Mild, Moderate and Severe Hepatic Impairment

Further study details as provided by AstraZeneca:

Primary Outcome Measures:

To characterise the pharmacokinetic profile of ZD4054 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:

To assess the safety of ZD4054 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 ]
To explore changes in protein binding of ZD4054 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
Estimated Study Completion Date:	April 2009
Estimated Primary Completion Date:	February 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Control (healthy volunteers)	Drug: ZD4054 10mg, Oral tablet, single dose
2: Experimental Mild Hepatic Impairment	Drug: ZD4054 10mg, Oral tablet, single dose
3: Experimental Moderate Hepatic Impairment	Drug: ZD4054 10mg, Oral tablet, single dose
4: Experimental Severe Hepatic Impairment	Drug: ZD4054 10mg, Oral tablet, single dose

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

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

Contacts

Contact: AstraZeneca Clinical Study Information

1-800-236-9933

information.center@astrazeneca.com

Locations

Czech Republic
Research Site	Recruiting
Praha 4, Czech Republic
Research Site	Recruiting
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

Responsible Party:	AstraZeneca Pharmaceuticals ( Thomas Morris, Medical Science Director, ZD4054 )
Study ID Numbers:	D4320C00025, 4054IL/0025
Study First Received:	May 1, 2008
Last Updated:	November 12, 2008
ClinicalTrials.gov Identifier:	NCT00672581
Health Authority:	United States: Food and Drug Administration; Czech Republic: State Institute for Drug Control

Keywords provided by AstraZeneca:

Hepatic Impairment

Study placed in the following topic categories:

Liver Diseases
Digestive System Diseases
Healthy

ClinicalTrials.gov processed this record on January 16, 2009