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

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

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

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.