Evaluation Of Hepatic Impairment On AG-013736 Pharmacokinetics

A Phase 1 Study To Evaluate The Pharmacokinetics Of AG-013736 In Subjects With Impaired Hepatic Function

This study will evaluate the effects of mild and moderate impairment of hepatic function on the single-dose pharmacokinetics, safety and tolerability of AG-013736.

Study Overview

• Status: Completed
• Conditions: Hepatic Insufficiency
• Intervention / Treatment: Drug: AG-013736

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33169
      • Pfizer Investigational Site
    • Orlando, Florida, United States, 32809
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of reduced hepatic function (Child Pugh Classification A or B)
• Body Mass Index of 18-32 kg/m2

Exclusion Criteria:

• History of febrile illness within 5 days prior to first dose
• Any condition possibly affecting drug absorption (e.g. gastrectomy)
• Positive urine drug screen

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Hepatic Function - Mild Impairment; Subjects with mild hepatic impairment (Child Pugh class A, score 5-6)	Drug: AG-013736; Single oral 5-mg dose of AG-013736, administered as a film-coated, immediate-release tablet.
EXPERIMENTAL: Hepatic Function - Moderate Impairment; Subjects with moderate hepatic impairment(Child Pugh class B,score 7-9)	Drug: AG-013736; Single oral 5-mg dose of AG-013736, administered as a film-coated, immediate-release tablet.
EXPERIMENTAL: Hepatic Function - Normal; Group 1 1) subjects with normal hepatic function	Drug: AG-013736; Single oral 5-mg dose of AG-013736, administered as a film-coated, immediate-release tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax)		0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hours (hrs) post-dose
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]	AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Time to Reach Maximum Observed Plasma Concentration (Tmax)		0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Plasma Elimination Half-life (t1/2)	Plasma elimination half-life is the time measured for the plasma concentration to decrease by one half.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Apparent Oral Clearance (CL/F)	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the oral bioavailability. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Apparent Volume of Distribution (Vz/F)	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the oral bioavailability.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Fraction of Unbound Drug (fu)	Fraction of unbound drug (fu) is defined as the ratio of unbound drug concentration to the total drug concentration.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Unbound Apparent Oral Clearance (CLu/F)	Clearance of an unbound drug is a measure of the rate at which an unbound drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the oral bioavailability. Unbound drug clearance is a quantitative measure of the rate at which an unbound drug substance is removed from the blood.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Unbound Apparent Volume of Distribution (Vzu/F)	Volume of distribution of unbound drug is defined as the theoretical volume in which the total amount of unbound drug would need to be uniformly distributed to produce the desired plasma concentration of unbound drug. Unbound apparent volume of distribution after oral dose (Vzu/F) is influenced by the oral bioavailability.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Unbound Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)u]	AUC (0 - ∞)u = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞) for unbound drug. It is obtained from AUCu (0 - t) plus AUCu (t - ∞).	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Unbound Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClastu)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClastu) for unbound drug.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose
Unbound Maximum Observed Plasma Concentration (Cmaxu)	Cmaxu is the highest measured unbound plasma concentration during the dosing interval.	0 (pre-dose), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 12, 16, 24, 36, 48, 96 and 144 hrs post-dose

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (ACTUAL): October 1, 2008
• Study Completion (ACTUAL): October 1, 2008

Study Registration Dates

• First Submitted: June 4, 2008
• First Submitted That Met QC Criteria: June 4, 2008
• First Posted (ESTIMATE): June 6, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): April 11, 2012
• Last Update Submitted That Met QC Criteria: April 5, 2012
• Last Verified: April 1, 2012

More Information

Terms related to this study

• Keywords: hepatic impairment
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Axitinib
• Other Study ID Numbers: A4061036