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

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Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Healthy Otherwise Healthy Volunteers With Mild or Moderate Hepatic Dysfunction

Interventions

dacomitinibDRUG

Subjects to receive 30 mg tablets of dacomitinib on Day 1 of Period 1.

dacomitinibDRUG

Subjects to receive 30 mg tablets of dacomitinib on Day 1 of Period 1.

dacomitinibDRUG

Subjects to receive 30 mg tablets of dacomitinib on Day 1 of Period 1.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 74 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (2)

Pfizer Investigational Site

Anaheim, California, United States

Pfizer Investigational Site

South Miami, Florida, United States

Outcomes

Primary Outcomes

Maximum Observed Plasma Concentration (Cmax)

Maximal plasma concentration (Cmax) for dacomitinib

Time frame: 2 weeks

Plasma area under plasma concentration-time curve from time zero to time infinity post dose (AUCinf) for dacomitinib

Time frame: 2 weeks

Secondary Outcomes

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

AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.

Time frame: 2 weeks

Plasma area under plasma concentration-time curve from time zero to 216 hours post dose (AUC216) for dacomitinib

Time frame: 2 weeks

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

Time of first observed maximal plasma concentration (Tmax) for dacomitinib

Time frame: 2 weeks

Plasma elimination half life (t1/2) of dacomitinib

Time frame: 2 weeks

Apparent plasma clearance (CL/F) of dacomitinib

Time frame: 2 weeks

Apparent volume of distribution (Vz/F) of dacomitinib

Time frame: 2 weeks

Data from ClinicalTrials.gov

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