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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01419041
First received: August 16, 2011
Last updated: September 28, 2012
Last verified: September 2012
  Purpose

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


Condition Intervention Phase
Renal Impairment
Drug: crizotinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Phase I, Single Dose, Parallel-Group Study To Evaluate The Pharmacokinetics Of Crizotinib (PF-02341066) In Subjects With Impaired Renal Function

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Plasma AUCinf (Area under the plasma concentration versus time curve from zero to infinity) for crizotinib [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Plasma Cmax (Maximum plasma concentration) for crizotinib [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma AUClast (Area under the plasma concentration versus time curve from zero to the last quantifiable concentration) for crizotinib [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Tmax (Time to Cmax) for crizotinib [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • t1/2 (terminal half-life) for crizotinib [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • CL/F (Apparent oral clearance) for crizotinib [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Vz/F (Apparent volume of distribution after oral dose) for crizotinib [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • fu (fraction of unbound drug in plasma) for crizotinib [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • AUCinf,u (unbound AUCinf) for crizotinib [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • AUClast,u (unbound AUClast) for crizotinib [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Cmax,u (unbound Cmax) for crizotinib [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • CL/Fu (unbound apparent oral clearance) for crizotinib [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • CLR (Renal clearance) for crizotinib [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Ae (Cumulative amount of drug recovered unchanged in the urine) for crizotinib [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Ae% (Cumulative amount of drug recovered unchanged in the urine expressed as fraction of administered dose) for crizotinib [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • AUCinf (Area under the plasma concentration versus time curve from zero to infinity) for PF-06260182 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • AUClast (Area under the plasma concentration versus time curve from zero to the last quantifiable concentration) for PF-06260182 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Cmax (Maximum plasma concentration) for PF-06260182 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Tmax (Time to Cmax) for PF-06260182 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • t1/2 (terminal half-life) for PF-06260182 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • fu (fraction of unbound drug in plasma) for PF-06260182 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • AUCinf,u (unbound AUCinf) for PF-06260182 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • AUClast,u (unbound AUClast) for PF-06260182 [ Time Frame: 18 months ] [ Designated as safety issue: No ]
  • Cmax,u (unbound Cmax) for PF-06260182 [ Time Frame: 18 months ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: November 2011
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Arm A
CLCR: Creatinine clearance
Drug: crizotinib
Single-dose oral 250 mg crizotinib in subjects with normal renal function (CLcr =>90 mL/min)
Arm B
CLCR: Creatinine clearance
Drug: crizotinib
Single-dose oral 250 mg crizotinib in subjects with severe renal impairment (CLcr <30 mL/min)

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01419041

Locations
United States, California
Pfizer Investigational Site
Anaheim, California, United States, 92801
United States, Florida
Pfizer Investigational Site
DeLand, Florida, United States, 32720
United States, Minnesota
Pfizer Investigational Site
Saint Paul, Minnesota, United States, 55114
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01419041     History of Changes
Other Study ID Numbers: A8081020
Study First Received: August 16, 2011
Last Updated: September 28, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
renal impairment
crizotinib
pharmacokinetics

Additional relevant MeSH terms:
Renal Insufficiency
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on July 20, 2014