Evaluation Of Hepatic Impairment On AG-013736 Pharmacokinetics

Phase 1

Completed

• Conditions: Hepatic Insufficiency
• Interventions: Drug: AG-013736

• Registration Number: NCT00692341
• Lead Sponsor: Pfizer

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2008-05
• Study First Submitted: 2008-06-04
• Study First Submitted QC: 2008-06-04
• Study First Posted: 2008-06-06
• Primary Completion: 2008-10
• Study Completion: 2008-10
• Results First Submitted: 2012-02-25
• Results First Submitted QC: 2012-02-25
• Results First Posted: 2012-03-27
• Status Verified: 2012-04
• Last Update Submitted: 2012-04-05
• Last Update Posted: 2012-04-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hepatic Function - Moderate Impairment	AG-013736	Subjects with moderate hepatic impairment(Child Pugh class B,score 7-9)
Hepatic Function - Normal	AG-013736	Group 1 1) subjects with normal hepatic function
Hepatic Function - Mild Impairment	AG-013736	Subjects with mild hepatic impairment (Child Pugh class A, score 5-6)

Primary Outcome Measures

Name	Time	Method
Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]	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	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 - ∞).
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

Secondary Outcome Measures

Name	Time	Method
Apparent Oral Clearance (CL/F)	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	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.
Area Under the Curve From Time Zero to Last Quantifiable 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	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).
Apparent Volume of Distribution (Vz/F)	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	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.
Fraction of Unbound Drug (fu)	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) is defined as the ratio of unbound drug concentration to the total drug concentration.
Unbound Maximum Observed Plasma Concentration (Cmaxu)	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	Cmaxu is the highest measured unbound plasma concentration during the dosing interval.
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)	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 is the time measured for the plasma concentration to decrease by one half.
Unbound Apparent Volume of Distribution (Vzu/F)	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	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.
Unbound Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)u]	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	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 - ∞).
Unbound Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClastu)	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	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClastu) for unbound drug.
Unbound Apparent Oral Clearance (CLu/F)	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	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.

Trial Locations

Locations (1)

Pfizer Investigational Site; 🇺🇸 Orlando, Florida, United States