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Relative Bioavailability Of A Crizotinib Oral Liquid Formulation To Crizotinib Formulated Capsule

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01297595
First received: February 15, 2011
Last updated: February 15, 2012
Last verified: February 2012
History of Changes
Results First Received: January 5, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Crossover Assignment;   Masking: Open Label;   Primary Purpose: Basic Science
Condition: Healthy
Intervention: Drug: crizotinib

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Crizotinib 250 mg FC First, Then Crizotinib 250 mg OLF Single oral dose of crizotinib 250 milligram (mg) formulated capsule (FC) in first intervention period; and single oral dose of crizotinib 250 mg oral liquid formulation (OLF) in second intervention period. A washout period of at least 14 days was maintained between each crizotinib dose.
Crizotinib 250 mg OLF First, Then Crizotinib 250 mg FC Single oral dose of crizotinib 250 mg OLF in first intervention period; and single oral dose of crizotinib 250 mg FC in second intervention period. A washout period of at least 14 days was maintained between each crizotinib dose.

Participant Flow for 3 periods

 Period 1:   First Intervention Period
    Crizotinib 250 mg FC First, Then Crizotinib 250 mg OLF     Crizotinib 250 mg OLF First, Then Crizotinib 250 mg FC  
STARTED     11     11  
COMPLETED     11     11  
NOT COMPLETED     0     0  

Period 2:   Washout Period (At Least 14 Days)
    Crizotinib 250 mg FC First, Then Crizotinib 250 mg OLF     Crizotinib 250 mg OLF First, Then Crizotinib 250 mg FC  
STARTED     11     11  
COMPLETED     11     11  
NOT COMPLETED     0     0  

Period 3:   Second Intervention Period
    Crizotinib 250 mg FC First, Then Crizotinib 250 mg OLF     Crizotinib 250 mg OLF First, Then Crizotinib 250 mg FC  
STARTED     11     11  
COMPLETED     11     11  
NOT COMPLETED     0     0  



  Baseline Characteristics
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Reporting Groups
  Description
Entire Study Population Includes participants randomized to receive crizotinib 250 mg FC first and crizotinib 250 mg OLF first.

Baseline Measures
    Entire Study Population  
Number of Participants  
[units: participants]
 		  22  
Age  
[units: years]
Mean ± Standard Deviation 		  38.0  ± 11.9  
Gender  
[units: participants]
 		 
Female     0  
Male     22  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Area Under the Curve From Time Zero to Infinite Time [AUC (0 - ∞)]   [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hours (hrs) post crizotinib dose ]
  Hide Outcome Measure 1

Measure Type Primary
Measure Title Area Under the Curve From Time Zero to Infinite Time [AUC (0 - ∞)]
Measure Description AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time Frame 0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hours (hrs) post crizotinib dose  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Pharmacokinetic (PK) parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.

Reporting Groups
  Description
Crizotinib 250 mg FC Single oral dose of crizotinib 250 mg FC [Reference] in either first intervention period or second intervention period.
Crizotinib 250 mg OLF Single oral dose of crizotinib 250 mg OLF [Test] in either first intervention period or second intervention period.

Measured Values
    Crizotinib 250 mg FC     Crizotinib 250 mg OLF  
Number of Participants Analyzed  
[units: participants]
 		  22     22  
Area Under the Curve From Time Zero to Infinite Time [AUC (0 - ∞)]  
[units: ng*hr/mL]
Geometric Mean ± Standard Deviation 		  2833  ± 1099     2821  ± 1086  


Statistical Analysis 1 for Area Under the Curve From Time Zero to Infinite Time [AUC (0 - ∞)]
Groups [1] All groups
Ratio of Adjusted Means [2] 99.58
90% Confidence Interval ( 91.08 to 108.87 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Natural log transformed AUC (0 - ∞) of crizotinib was analyzed using a mixed effect model with sequence, period and treatment as a fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. This was an estimation study and there was no formal statistical hypothesis.
[2] Other relevant estimation information:
  No text entered.



2.  Secondary:   Time to Reach Maximum Observed Plasma Concentration (Tmax)   [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 2

3.  Secondary:   Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)   [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 3

4.  Secondary:   Maximum Observed Plasma Concentration (Cmax)   [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 4

5.  Secondary:   Plasma Terminal Half-Life (t1/2)   [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 5

6.  Secondary:   Apparent Oral Clearance (CL/F)   [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 6

7.  Secondary:   Apparent Volume of Distribution (Vz/F)   [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 7

8.  Secondary:   Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182)   [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 8

9.  Secondary:   Area Under the Curve From Time Zero to Infinite Time [AUC (0 - ∞)] for Crizotinib Metabolite (PF-06260182)   [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 9

10.  Secondary:   Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182)   [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 10

11.  Secondary:   Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182)   [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 11

12.  Secondary:   Metabolite to Parent Ratio of Maximum Observed Plasma Concentration (MRCmax)   [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 12

13.  Secondary:   Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Last Quantifiable Concentration (MRAUClast)   [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 13

14.  Secondary:   Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Infinite Time [MRAUC (0- ∞)]   [ Time Frame: 0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 14


  Serious Adverse Events
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  Other Adverse Events
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  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


No publications provided


Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01297595     History of Changes
Other Study ID Numbers: A8081019
Study First Received: February 15, 2011
Results First Received: January 5, 2012
Last Updated: February 15, 2012
Health Authority: United States: Food and Drug Administration