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.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: crizotinib; Drug: crizotinib

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Anaheim, California, United States, 92801
      • Pfizer Investigational Site
  • Florida
    • DeLand, Florida, United States, 32720
      • Pfizer Investigational Site
  • Minnesota
    • Saint Paul, Minnesota, United States, 55114
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): August 1, 2012

Study Registration Dates

• First Submitted: August 16, 2011
• First Submitted That Met QC Criteria: August 16, 2011
• First Posted (ESTIMATE): August 17, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): October 1, 2012
• Last Update Submitted That Met QC Criteria: September 28, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: pharmacokinetics; renal impairment; crizotinib
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Crizotinib
• Other Study ID Numbers: A8081020