Clinical trial NCT01419041: A Study to Evaluate The Pharmacokinetics Of Crizotinib (PF-02341066) In Subjects With Impaired Renal Function
Official title: A Phase I, Single Dose, Parallel-Group Study To Evaluate The Pharmacokinetics Of Crizotinib (PF-02341066) In Subjects With Impaired Renal Function
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Keywords: renal impairment
crizotinib
pharmacokinetics
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-08-17
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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


Eligibility 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.

Primary outcomes:
measure: Plasma AUCinf (Area under the plasma concentration versus time curve from zero to infinity) for crizotinib
timeFrame: 18 months
measure: Plasma Cmax (Maximum plasma concentration) for crizotinib
timeFrame: 18 months
Secondary outcomes:
measure: Plasma AUClast (Area under the plasma concentration versus time curve from zero to the last quantifiable concentration) for crizotinib
timeFrame: 18 months
measure: Tmax (Time to Cmax) for crizotinib
timeFrame: 18 months
measure: t1/2 (terminal half-life) for crizotinib
timeFrame: 18 months
measure: CL/F (Apparent oral clearance) for crizotinib
timeFrame: 18 months
measure: Vz/F (Apparent volume of distribution after oral dose) for crizotinib
timeFrame: 18 months
measure: fu (fraction of unbound drug in plasma) for crizotinib
timeFrame: 18 months
measure: AUCinf,u (unbound AUCinf) for crizotinib
timeFrame: 18 months
measure: AUClast,u (unbound AUClast) for crizotinib
timeFrame: 18 months
measure: Cmax,u (unbound Cmax) for crizotinib
timeFrame: 18 months
measure: CL/Fu (unbound apparent oral clearance) for crizotinib
timeFrame: 18 months
measure: CLR (Renal clearance) for crizotinib
timeFrame: 18 months
measure: Ae (Cumulative amount of drug recovered unchanged in the urine) for crizotinib
timeFrame: 18 months
measure: Ae% (Cumulative amount of drug recovered unchanged in the urine expressed as fraction of administered dose) for crizotinib
timeFrame: 18 months
measure: AUCinf (Area under the plasma concentration versus time curve from zero to infinity) for PF-06260182
timeFrame: 18 months
measure: AUClast (Area under the plasma concentration versus time curve from zero to the last quantifiable concentration) for PF-06260182
timeFrame: 18 months
measure: Cmax (Maximum plasma concentration) for PF-06260182
timeFrame: 18 months
measure: Tmax (Time to Cmax) for PF-06260182
timeFrame: 18 months
measure: t1/2 (terminal half-life) for PF-06260182
timeFrame: 18 months
measure: fu (fraction of unbound drug in plasma) for PF-06260182
timeFrame: 18 months
measure: AUCinf,u (unbound AUCinf) for PF-06260182
timeFrame: 18 months
measure: AUClast,u (unbound AUClast) for PF-06260182
timeFrame: 18 months
measure: Cmax,u (unbound Cmax) for PF-06260182
timeFrame: 18 months
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Pfizer Investigational Site
state: California
city: DeLand
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Saint Paul
country: United States
facility: Pfizer Investigational Site
state: Minnesota
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: