Evaluation Of Hepatic Impairment On AG-013736 Pharmacokinetics

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00692341
First received: June 4, 2008
Last updated: April 5, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Hepatic Insufficiency
Drug: AG-013736
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: A Phase 1 Study To Evaluate The Pharmacokinetics Of AG-013736 In Subjects With Impaired Hepatic Function

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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 - ∞).


Secondary Outcome Measures:
  • Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast).

  • Time to Reach Maximum Observed Plasma Concentration (Tmax) [ Time Frame: 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 ] [ Designated as safety issue: No ]
  • Plasma Elimination Half-life (t1/2) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Plasma elimination half-life is the time measured for the plasma concentration to decrease by one half.

  • Apparent Oral Clearance (CL/F) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Apparent Volume of Distribution (Vz/F) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Fraction of unbound drug (fu) is defined as the ratio of unbound drug concentration to the total drug concentration.

  • Unbound Apparent Oral Clearance (CLu/F) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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.

  • Unbound Apparent Volume of Distribution (Vzu/F) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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] [ Time Frame: 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 ] [ Designated as safety issue: No ]
    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) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Area under the plasma concentration time-curve from zero to the last measured concentration (AUClastu) for unbound drug.

  • Unbound Maximum Observed Plasma Concentration (Cmaxu) [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Cmaxu is the highest measured unbound plasma concentration during the dosing interval.


Enrollment: 24
Study Start Date: May 2008
Study Completion Date: October 2008
Primary Completion Date: October 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  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: NCT00692341

Locations
United States, Florida
Pfizer Investigational Site
Miami, Florida, United States, 33169
Pfizer Investigational Site
Orlando, Florida, United States, 32809
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00692341     History of Changes
Other Study ID Numbers: A4061036
Study First Received: June 4, 2008
Results First Received: February 25, 2012
Last Updated: April 5, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
hepatic impairment

Additional relevant MeSH terms:
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Axitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014