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

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

Official Title
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A Phase I, Single Dose, Parallel-Group Study To Evaluate The Pharmacokinetics Of Crizotinib (PF-02341066) In Subjects With Impaired Renal Function

Conditions
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Renal Impairment

Intervention / Treatment
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* Drug: crizotinib
* Drug: crizotinib


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Arm A<br>CLCR: Creatinine clearance | Drug: crizotinib<br>* Single-dose oral 250 mg crizotinib in subjects with normal renal function (CLcr =>90 mL/min)<br>|
| Other: Arm B<br>CLCR: Creatinine clearance | Drug: crizotinib<br>* Single-dose oral 250 mg crizotinib in subjects with severe renal impairment (CLcr <30 mL/min)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma AUCinf (Area under the plasma concentration versus time curve from zero to infinity) for crizotinib |  | 18 months | 
| Plasma Cmax (Maximum plasma concentration) for crizotinib |  | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma AUClast (Area under the plasma concentration versus time curve from zero to the last quantifiable concentration) for crizotinib |  | 18 months | 
| Tmax (Time to Cmax) for crizotinib |  | 18 months | 
| t1/2 (terminal half-life) for crizotinib |  | 18 months | 
| CL/F (Apparent oral clearance) for crizotinib |  | 18 months | 
| Vz/F (Apparent volume of distribution after oral dose) for crizotinib |  | 18 months | 
| fu (fraction of unbound drug in plasma) for crizotinib |  | 18 months | 
| AUCinf,u (unbound AUCinf) for crizotinib |  | 18 months | 
| AUClast,u (unbound AUClast) for crizotinib |  | 18 months | 
| Cmax,u (unbound Cmax) for crizotinib |  | 18 months | 
| CL/Fu (unbound apparent oral clearance) for crizotinib |  | 18 months | 
| CLR (Renal clearance) for crizotinib |  | 18 months | 
| Ae (Cumulative amount of drug recovered unchanged in the urine) for crizotinib |  | 18 months | 
| Ae% (Cumulative amount of drug recovered unchanged in the urine expressed as fraction of administered dose) for crizotinib |  | 18 months | 
| AUCinf (Area under the plasma concentration versus time curve from zero to infinity) for PF-06260182 |  | 18 months | 
| AUClast (Area under the plasma concentration versus time curve from zero to the last quantifiable concentration) for PF-06260182 |  | 18 months | 
| Cmax (Maximum plasma concentration) for PF-06260182 |  | 18 months | 
| Tmax (Time to Cmax) for PF-06260182 |  | 18 months | 
| t1/2 (terminal half-life) for PF-06260182 |  | 18 months | 
| fu (fraction of unbound drug in plasma) for PF-06260182 |  | 18 months | 
| AUCinf,u (unbound AUCinf) for PF-06260182 |  | 18 months | 
| AUClast,u (unbound AUClast) for PF-06260182 |  | 18 months | 
| Cmax,u (unbound Cmax) for PF-06260182 |  | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renal impairment, crizotinib, pharmacokinetics