A Study To Compare Pharmacokinetics Of Dacomitinib (PF-00299804) Between Healthy Subjects And Subjects With Mild And Moderate Hepatic Impairment
- Conditions
- HealthyOtherwise Healthy Volunteers With Mild or Moderate Hepatic Dysfunction
- Interventions
- Registration Number
- NCT01571388
- Lead Sponsor
- Pfizer
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 25
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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.
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Body Mass Index (BMI) of 18 to 35 kg/m2;
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An informed consent document signed and dated by the subject.
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Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
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Subjects in the normal hepatic function group (Group 1): No known or suspected hepatic impairment.
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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.
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Any condition possibly affecting drug absorption (eg, gastrectomy, chronic diarrhea, rapid transit).
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A positive urine drug screen.
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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].
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Group 1 dacomitinib Healthy Subjects to receive dacomitinib Group 2 dacomitinib Subjects with mildly impaired hepatic function to receive dacomitinib Group 3 dacomitinib Subjects with moderately impaired hepatic function to receive dacomitinib
- Primary Outcome Measures
Name Time Method Maximum Observed Plasma Concentration (Cmax) 2 weeks Maximal plasma concentration (Cmax) for dacomitinib
Plasma area under plasma concentration-time curve from time zero to time infinity post dose (AUCinf) for dacomitinib 2 weeks
- Secondary Outcome Measures
Name Time Method Time of first observed maximal plasma concentration (Tmax) for dacomitinib 2 weeks Plasma elimination half life (t1/2) of dacomitinib 2 weeks Apparent plasma clearance (CL/F) of dacomitinib 2 weeks Apparent volume of distribution (Vz/F) of dacomitinib 2 weeks Fraction of unbound dacomitinib in plasma (fu) 2 weeks Unbound apparent plasma clearance (CL/F) of dacomitinib , 2 weeks Unbound apparent volume of distribution (Vz/F) of dacomitinib 2 weeks Plasma area under plasma concentration-time curve from time zero to time of last quantifiable concentration post dose (AUClast) for PF-05199265 2 weeks Overall safety profile as characterized by laboratory abnormalities, observed physical examination, vital signs, ECGs, and adverse event monitoring. 6-8 weeks Maximal unbound plasma concentration (Cmax) for PF-05199265 2 weeks 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 2 weeks 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 2 weeks Plasma area under plasma concentration-time curve from time zero to time of last quantifiable concentration post dose (AUClast) for dacomitinib 2 weeks Maximal plasma concentration (Cmax) for PF-05199265 2 weeks Time of first observed maximal plasma concentration (Tmax) for PF-05199265 2 weeks Metabolite ratio for plasma area under plasma concentration-time curve from time zero to time infinity post dose (MRAUCinf) 2 weeks Metabolite ratio for plasma area under plasma concentration-time curve from time zero to time of last quantifiable concentration post dose (MRAUClast) 2 weeks Metabolite ratio for maximal plasma concentration (MRCmax) 2 weeks Fraction of unbound PF-05199265 in plasma (fu) 2 weeks Unbound plasma area under plasma concentration-time curve from time zero to 24 hours post dose (AUC24) for PF-05199265 2 weeks Unbound plasma area under plasma concentration-time curve from time zero to 216 hours post dose (AUC216) for PF-05199265 2 weeks Unbound plasma area under plasma concentration-time curve from time zero to time of last quantifiable concentration post dose (AUClast) for PF-05199265 2 weeks Unbound Plasma area under plasma concentration-time curve from time zero to time infinity post dose (AUCinf) for PF-05199265 2 weeks Unbound Plasma area under plasma concentration-time curve from time zero to time infinity post dose (AUCinf) for dacomitinib 2 weeks Unbound plasma area under plasma concentration-time curve from time zero to 24 hours post dose (AUC24) for dacomitinib 2 weeks Unbound plasma area under plasma concentration-time curve from time zero to 216 hours post dose (AUC216) for dacomitinib 2 weeks Unbound plasma area under plasma concentration-time curve from time zero to time of last quantifiable concentration post dose (AUClast) for dacomitinib 2 weeks Maximal unbound plasma concentration (Cmax) for dacomitinib 2 weeks Plasma area under plasma concentration-time curve from time zero to time infinity post dose (AUCinf) for PF-05199265 2 weeks Plasma area under plasma concentration-time curve from time zero to 24 hours post dose (AUC24) for PF-05199265 2 weeks Plasma area under plasma concentration-time curve from time zero to 216 hours post dose (AUC216) for PF-05199265 2 weeks
Trial Locations
- Locations (1)
Pfizer Investigational Site
🇺🇸South Miami, Florida, United States