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Bioequivalence And Food Effect Study Comparing The Commercial Formulation Of Crizotinib To Its Clinical Study Formulations And Commercial Formulation With Or Without Food In Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01154218
First received: June 29, 2010
Last updated: October 20, 2011
Last verified: October 2011
History of Changes
Results First Received: September 12, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Crossover Assignment;   Masking: Open Label
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
No text entered.

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 IRT Fasted, PIC Fasted, CIC Fasted, CIC Fed Single oral dose of crizotinib 250 milligram (mg) immediate release tablet (IRT) in fasted state in first intervention period; followed by single oral dose of crizotinib 250 mg powder in capsule (PIC) in fasted state in second intervention period; followed by single oral dose of crizotinib 250 mg commercial image capsule (CIC) in fasted state in third intervention period; and single oral dose of crizotinib 250 mg CIC in fed state in fourth intervention period. A washout period of at least 14 days was maintained between each period.
Crizotinib 250 mg PIC Fasted, CIC Fed, IRT Fasted, CIC Fasted Single oral dose of crizotinib 250 mg PIC in fasted state in first intervention period; followed by single oral dose of crizotinib 250 mg CIC in fed state in second intervention period; followed by single oral dose of crizotinib 250 mg IRT in fasted state in third intervention period; and single oral dose of crizotinib 250 mg CIC in fasted state in fourth intervention period. A washout period of at least 14 days was maintained between each period.
Crizotinib 250 mg CIC Fasted, IRT Fasted, CIC Fed, PIC Fasted Single oral dose of crizotinib 250 mg CIC in fasted state in first intervention period; followed by single oral dose of crizotinib 250 mg IRT in fasted state in second intervention period; followed by single oral dose of crizotinib 250 mg CIC in fed state in third intervention period; and single oral dose of crizotinib 250 mg PIC in fasted state in fourth intervention period. A washout period of at least 14 days was maintained between each period.
Crizotinib 250 mg CIC Fed, CIC Fasted, PIC Fasted, IRT Fasted Single oral dose of crizotinib 250 mg CIC in fed state in first intervention period; followed by single oral dose of crizotinib 250 mg CIC in fasted state in second intervention period; followed by single oral dose of crizotinib 250 mg PIC in fasted state in third intervention period; and single oral dose of crizotinib 250 mg IRT in fasted state in fourth intervention period. A washout period of at least 14 days was maintained between each period.

Participant Flow for 7 periods

 Period 1:   First Intervention Period
    Crizotinib 250 mg IRT Fasted, PIC Fasted, CIC Fasted, CIC Fed     Crizotinib 250 mg PIC Fasted, CIC Fed, IRT Fasted, CIC Fasted     Crizotinib 250 mg CIC Fasted, IRT Fasted, CIC Fed, PIC Fasted     Crizotinib 250 mg CIC Fed, CIC Fasted, PIC Fasted, IRT Fasted  
STARTED     9     9     9     9  
COMPLETED     9     9     9     9  
NOT COMPLETED     0     0     0     0  

Period 2:   Washout Period (at Least 14 Days)
    Crizotinib 250 mg IRT Fasted, PIC Fasted, CIC Fasted, CIC Fed     Crizotinib 250 mg PIC Fasted, CIC Fed, IRT Fasted, CIC Fasted     Crizotinib 250 mg CIC Fasted, IRT Fasted, CIC Fed, PIC Fasted     Crizotinib 250 mg CIC Fed, CIC Fasted, PIC Fasted, IRT Fasted  
STARTED     9     9     9     9  
COMPLETED     9     9     9     9  
NOT COMPLETED     0     0     0     0  

Period 3:   Second Intervention Period
    Crizotinib 250 mg IRT Fasted, PIC Fasted, CIC Fasted, CIC Fed     Crizotinib 250 mg PIC Fasted, CIC Fed, IRT Fasted, CIC Fasted     Crizotinib 250 mg CIC Fasted, IRT Fasted, CIC Fed, PIC Fasted     Crizotinib 250 mg CIC Fed, CIC Fasted, PIC Fasted, IRT Fasted  
STARTED     9     9     9     9  
COMPLETED     9     9     9     9  
NOT COMPLETED     0     0     0     0  

Period 4:   Washout Period (at Least 14 Days)
    Crizotinib 250 mg IRT Fasted, PIC Fasted, CIC Fasted, CIC Fed     Crizotinib 250 mg PIC Fasted, CIC Fed, IRT Fasted, CIC Fasted     Crizotinib 250 mg CIC Fasted, IRT Fasted, CIC Fed, PIC Fasted     Crizotinib 250 mg CIC Fed, CIC Fasted, PIC Fasted, IRT Fasted  
STARTED     9     9     9     9  
COMPLETED     9     9     9     9  
NOT COMPLETED     0     0     0     0  

Period 5:   Third Intervention Period
    Crizotinib 250 mg IRT Fasted, PIC Fasted, CIC Fasted, CIC Fed     Crizotinib 250 mg PIC Fasted, CIC Fed, IRT Fasted, CIC Fasted     Crizotinib 250 mg CIC Fasted, IRT Fasted, CIC Fed, PIC Fasted     Crizotinib 250 mg CIC Fed, CIC Fasted, PIC Fasted, IRT Fasted  
STARTED     9     9     9     9  
COMPLETED     9     8     9     9  
NOT COMPLETED     0     1     0     0  
Adverse Event                 0                 1                 0                 0  

Period 6:   Washout Period (at Least 14 Days)
    Crizotinib 250 mg IRT Fasted, PIC Fasted, CIC Fasted, CIC Fed     Crizotinib 250 mg PIC Fasted, CIC Fed, IRT Fasted, CIC Fasted     Crizotinib 250 mg CIC Fasted, IRT Fasted, CIC Fed, PIC Fasted     Crizotinib 250 mg CIC Fed, CIC Fasted, PIC Fasted, IRT Fasted  
STARTED     9     8     9     9  
COMPLETED     9     8     9     8  
NOT COMPLETED     0     0     0     1  
Withdrawal by Subject                 0                 0                 0                 1  

Period 7:   Fourth Intervention Period
    Crizotinib 250 mg IRT Fasted, PIC Fasted, CIC Fasted, CIC Fed     Crizotinib 250 mg PIC Fasted, CIC Fed, IRT Fasted, CIC Fasted     Crizotinib 250 mg CIC Fasted, IRT Fasted, CIC Fed, PIC Fasted     Crizotinib 250 mg CIC Fed, CIC Fasted, PIC Fasted, IRT Fasted  
STARTED     9     8     9     8  
COMPLETED     8     8     9     8  
NOT COMPLETED     1     0     0     0  
Withdrawal by Subject                 1                 0                 0                 0  



  Baseline Characteristics
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Reporting Groups
  Description
Entire Study Population Includes participants randomized to receive any treatment (crizotinib 250 mg IRT fasted first, crizotinib 250 mg PIC fasted first, crizotinib 250 mg CIC fasted first and crizotinib 250 mg CIC fed).

Baseline Measures
    Entire Study Population  
Number of Participants  
[units: participants]
 		  36  
Age  
[units: years]
Mean ± Standard Deviation 		  38.9  ± 8.1  
Gender  
[units: participants]
 		 
Female     0  
Male     36  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞])   [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hours (hrs) post crizotinib dose ]
  Show Outcome Measure 1

2.  Primary:   Maximum Observed Plasma Concentration (Cmax)   [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 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, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 3

4.  Secondary:   Time to Reach Maximum Observed Plasma Concentration (Tmax)   [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 4

5.  Secondary:   Plasma Decay Half Life (t1/2)   [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 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, 4, 5, 6, 8, 10, 12, 24, 36, 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, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Hide Outcome Measure 7

Measure Type Secondary
Measure Title Apparent Volume of Distribution (Vz/F)
Measure Description Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Time Frame 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 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.
PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.

Reporting Groups
  Description
Crizotinib IRT Fasted Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period.
Crizotinib PIC Fasted Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period.
Crizotinib CIC Fasted Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period.
Crizotinib CIC Fed Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period.

Measured Values
    Crizotinib IRT Fasted     Crizotinib PIC Fasted     Crizotinib CIC Fasted     Crizotinib CIC Fed  
Number of Participants Analyzed  
[units: participants]
 		  35     35     35     36  
Apparent Volume of Distribution (Vz/F)  
[units: L]
Geometric Mean ± Standard Deviation 		  4290.0  ± 1672.4     4703.0  ± 2874.7     4313.0  ± 3880.9     5096.0  ± 2302.0  

No statistical analysis provided for Apparent Volume of Distribution (Vz/F)



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, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 8

9.  Secondary:   Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) for Crizotinib Metabolite (PF-06260182)   [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 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, 4, 5, 6, 8, 10, 12, 24, 36, 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, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose ]
  Show Outcome Measure 11


  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: NCT01154218     History of Changes
Other Study ID Numbers: A8081011
Study First Received: June 29, 2010
Results First Received: September 12, 2011
Last Updated: October 20, 2011
Health Authority: United States: Food and Drug Administration