A Study To Compare Pharmacokinetics Of Dacomitinib (PF-00299804) Between Healthy Subjects And Subjects With Mild And Moderate Hepatic Impairment

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01571388
First received: April 3, 2012
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

The study will determine if there are differences in how dacomitinib is absorbed and eliminated between healthy subjects and subjects with mild and moderately impaired hepatic function.


Condition Intervention Phase
Healthy
Otherwise Healthy Volunteers With Mild or Moderate Hepatic Dysfunction
Drug: dacomitinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Phase 1 Study To Evaluate The Single Dose Pharmacokinetics Of Dacomitinib (PF-00299804) In Subjects With Impaired Hepatic Function

Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Maximum Observed Plasma Concentration (Cmax) [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    Maximal plasma concentration (Cmax) for dacomitinib

  • Plasma area under plasma concentration-time curve from time zero to time infinity post dose (AUCinf) for dacomitinib [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Area under the Concentration-Time Curve (AUC);Plasma area under plasma concentration-time curve from time zero to 24 hours post dose (AUC24) for dacomitinib [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
    AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.

  • Plasma area under plasma concentration-time curve from time zero to 216 hours post dose (AUC216) for dacomitinib [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Plasma area under plasma concentration-time curve from time zero to time of last quantifiable concentration post dose (AUClast) for dacomitinib [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Time of first observed maximal plasma concentration (Tmax) for dacomitinib [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Plasma elimination half life (t1/2) of dacomitinib [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Apparent plasma clearance (CL/F) of dacomitinib [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Apparent volume of distribution (Vz/F) of dacomitinib [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Fraction of unbound dacomitinib in plasma (fu) [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Unbound apparent plasma clearance (CL/F) of dacomitinib , [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Unbound apparent volume of distribution (Vz/F) of dacomitinib [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Unbound Plasma area under plasma concentration-time curve from time zero to time infinity post dose (AUCinf) for dacomitinib [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Unbound plasma area under plasma concentration-time curve from time zero to 24 hours post dose (AUC24) for dacomitinib [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Unbound plasma area under plasma concentration-time curve from time zero to 216 hours post dose (AUC216) for dacomitinib [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Unbound plasma area under plasma concentration-time curve from time zero to time of last quantifiable concentration post dose (AUClast) for dacomitinib [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Maximal unbound plasma concentration (Cmax) for dacomitinib [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Plasma area under plasma concentration-time curve from time zero to time infinity post dose (AUCinf) for PF-05199265 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Plasma area under plasma concentration-time curve from time zero to 24 hours post dose (AUC24) for PF-05199265 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Plasma area under plasma concentration-time curve from time zero to 216 hours post dose (AUC216) for PF-05199265 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Plasma area under plasma concentration-time curve from time zero to time of last quantifiable concentration post dose (AUClast) for PF-05199265 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Maximal plasma concentration (Cmax) for PF-05199265 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Time of first observed maximal plasma concentration (Tmax) for PF-05199265 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Metabolite ratio for plasma area under plasma concentration-time curve from time zero to time infinity post dose (MRAUCinf) [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Metabolite ratio for plasma area under plasma concentration-time curve from time zero to time of last quantifiable concentration post dose (MRAUClast) [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Metabolite ratio for maximal plasma concentration (MRCmax) [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Fraction of unbound PF-05199265 in plasma (fu) [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Unbound plasma area under plasma concentration-time curve from time zero to 24 hours post dose (AUC24) for PF-05199265 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Unbound plasma area under plasma concentration-time curve from time zero to 216 hours post dose (AUC216) for PF-05199265 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Unbound plasma area under plasma concentration-time curve from time zero to time of last quantifiable concentration post dose (AUClast) for PF-05199265 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Unbound Plasma area under plasma concentration-time curve from time zero to time infinity post dose (AUCinf) for PF-05199265 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Maximal unbound plasma concentration (Cmax) for PF-05199265 [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]
  • Overall safety profile as characterized by laboratory abnormalities, observed physical examination, vital signs, ECGs, and adverse event monitoring. [ Time Frame: 6-8 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 25
Study Start Date: April 2012
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Healthy Subjects to receive dacomitinib
Drug: dacomitinib
Subjects to receive 30 mg tablets of dacomitinib on Day 1 of Period 1.
Experimental: Group 2
Subjects with mildly impaired hepatic function to receive dacomitinib
Drug: dacomitinib
Subjects to receive 30 mg tablets of dacomitinib on Day 1 of Period 1.
Experimental: Group 3
Subjects with moderately impaired hepatic function to receive dacomitinib
Drug: dacomitinib
Subjects to receive 30 mg tablets of dacomitinib on Day 1 of Period 1.

  Eligibility

Ages Eligible for Study:   18 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male and/or female subjects of non-childbearing potential between the ages of 18 years of age to <75 years of age. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests. Liver function tests, albumin and prothrombin time must be within normal range.
  • Body Mass Index (BMI) of 18 to 35 kg/m2;
  • An informed consent document signed and dated by the subject.
  • Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
  • Subjects in the normal hepatic function group (Group 1): No known or suspected hepatic impairment.
  • For subjects in the hepatic impairment groups (Groups 2 and 3):

    • Should satisfy the criteria for Class A or B of the modified Child-Pugh classification
    • A diagnosis of hepatic dysfunction due to hepatocellular disease (and not secondary to any acute ongoing hepatocellular process) documented by medical history, physical examination, liver biopsy, hepatic ultrasound, CT scan, or MRI.
    • Stable hepatic impairment, defined as no clinically significant change in disease status within the last 30 days, as documented by the subject's recent medical history
    • Must be on a stable dose of medication and/or treatment regimen.

Exclusion Criteria:

  • Any condition possibly affecting drug absorption (eg, gastrectomy, chronic diarrhea, rapid transit).
  • A positive urine drug screen.
  • Females of childbearing potential, including those with tubal ligation. [To be considered for enrollment, women of at least 45 years of age who are postmenopausal (defined as being amenorrheic for at least 2 years) must have confirmatory FSH test results at screening].
  • In addition, subjects in the hepatic impairment groups (Groups 2 and 3) presenting with any of the following will not be included in the trial:

    • Hepatic carcinoma and hepatorenal syndrome or life expectancy <1 year.
    • Undergone porta-caval shunt surgery.
    • History of gastrointestinal hemorrhage due to esophageal varices or peptic ulcers less than one month prior to study entry.
  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: NCT01571388

Locations
United States, California
Pfizer Investigational Site
Anaheim, California, United States, 92801
United States, Florida
Pfizer Investigational Site
South Miami, Florida, United States, 33143
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: NCT01571388     History of Changes
Other Study ID Numbers: A7471018
Study First Received: April 3, 2012
Last Updated: December 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
dacomitinib
PF-00299804
hepatic impairment
pharmacokinetics

ClinicalTrials.gov processed this record on September 29, 2014