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A Study to Evaluate The Pharmacokinetics Of Crizotinib (PF-02341066) In Subjects With Impaired Renal Function

Phase 1
Completed
Conditions
Renal Impairment
Interventions
Registration Number
NCT01419041
Lead Sponsor
Pfizer
Brief Summary

The present study is being conducted to evaluate whether or not severe renal impairment has an effect on crizotinib Pharmacokinetics.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
16
Inclusion Criteria

All Subjects

  • Healthy male and/or female of non childbearing potential subjects between the ages of 18 and 65 years, inclusive ('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).
  • Body Mass Index (BMI) of 18 to 40 kg/m2 inclusive; and a total body weight >50 kg (>110 lbs).

Subjects with Normal Renal Function (Group 1)

  • Normal renal function (CLcr =>90 mL/min) during the screening period.
  • Matched 1-to-1 to subjects in Group 2 with respect to age (+/-5 years), weight (+/-10 kg), gender, and race according to protocol.

Subjects with Severe Renal Impairment (Groups 2)

  • Good general health commensurate with the population with chronic kidney disease.
  • Severe renal impairment (CLcr<30 mL/min) during the screening period.
Exclusion Criteria

All Subjects

  • Renal allograft recipients.
  • Any condition possibly affecting drug absorption.
  • 12 lead ECG demonstrating QTc >470 msec at screening.
  • Urinary incontinence without catheterization.
  • A positive urine drug screen.
  • History of regular alcohol consumption.
  • Treatment with an investigational drug within 30 days (or as determined by the local requirement, whichever is longer) or 5 half lives preceding the first dose of study medication.
  • Pregnant or nursing females; females of childbearing potential, including those with tubal ligation.
  • Blood donation of approximately 1 pint (500 mL) within 56 days prior to dosing.

Subjects with Severe Renal Impairment (Groups 2)

  • Subjects with any significant hepatic, cardiac or pulmonary disease (apart from stable ischemic heart disease), or subjects who are clinically nephrotic.
  • Subjects requiring hemodialysis.
  • Subjects with strict fluid restriction (ie, <1500 mL/24 hours).
  • Significant bleeding diathesis which could preclude multiple venipuncture.
  • Use of food or drugs that are CYP3A4 inhibitors and inducers.
  • Herbal supplements and hormone replacement therapy must be discontinued 28 days prior to the first dose of trial medication
  • Concurrent use of drugs that are CYP3A4 substrates with narrow therapeutic indices.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm AcrizotinibCLCR: Creatinine clearance
Arm BcrizotinibCLCR: Creatinine clearance
Primary Outcome Measures
NameTimeMethod
Plasma AUCinf (Area under the plasma concentration versus time curve from zero to infinity) for crizotinib18 months
Plasma Cmax (Maximum plasma concentration) for crizotinib18 months
Secondary Outcome Measures
NameTimeMethod
AUCinf,u (unbound AUCinf) for PF-0626018218 months
AUClast,u (unbound AUClast) for PF-0626018218 months
Cmax,u (unbound Cmax) for PF-0626018218 months
Plasma AUClast (Area under the plasma concentration versus time curve from zero to the last quantifiable concentration) for crizotinib18 months
Tmax (Time to Cmax) for crizotinib18 months
t1/2 (terminal half-life) for crizotinib18 months
CL/F (Apparent oral clearance) for crizotinib18 months
Vz/F (Apparent volume of distribution after oral dose) for crizotinib18 months
fu (fraction of unbound drug in plasma) for crizotinib18 months
AUCinf,u (unbound AUCinf) for crizotinib18 months
AUClast,u (unbound AUClast) for crizotinib18 months
Cmax,u (unbound Cmax) for crizotinib18 months
CL/Fu (unbound apparent oral clearance) for crizotinib18 months
CLR (Renal clearance) for crizotinib18 months
Ae (Cumulative amount of drug recovered unchanged in the urine) for crizotinib18 months
Ae% (Cumulative amount of drug recovered unchanged in the urine expressed as fraction of administered dose) for crizotinib18 months
AUCinf (Area under the plasma concentration versus time curve from zero to infinity) for PF-0626018218 months
AUClast (Area under the plasma concentration versus time curve from zero to the last quantifiable concentration) for PF-0626018218 months
Cmax (Maximum plasma concentration) for PF-0626018218 months
Tmax (Time to Cmax) for PF-0626018218 months
t1/2 (terminal half-life) for PF-0626018218 months
fu (fraction of unbound drug in plasma) for PF-0626018218 months

Trial Locations

Locations (1)

Pfizer Investigational Site

🇺🇸

Saint Paul, Minnesota, United States

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