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

Pfizer

Status and phase: Completed; Phase 1

Conditions: Healthy; Otherwise Healthy Volunteers With Mild or Moderate Hepatic Dysfunction

Treatments: Drug: dacomitinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT01571388

A7471018

Details and patient eligibility

About

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.

Enrollment: 25 patients

Sex: All

Ages: 18 to 74 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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25 participants in 3 patient groups

Group 1

Experimental group

Description:

Healthy Subjects to receive dacomitinib

Treatment:

Drug: dacomitinib

Drug: dacomitinib

Drug: dacomitinib

Group 2

Experimental group

Description:

Subjects with mildly impaired hepatic function to receive dacomitinib

Treatment:

Drug: dacomitinib

Drug: dacomitinib

Drug: dacomitinib

Group 3

Experimental group

Description:

Subjects with moderately impaired hepatic function to receive dacomitinib

Treatment:

Drug: dacomitinib

Drug: dacomitinib

Drug: dacomitinib