A Phase 1 Absolute Bioavailability Study For Oral Crizotinib In Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01168934
First received: July 22, 2010
Last updated: October 20, 2011
Last verified: October 2011
Results First Received: September 12, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Parallel 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
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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 50 mg IV First, Then Crizotinib 250 mg Oral Single intravenous (IV) dose of crizotinib 50 milligram (mg) in first intervention period; and single oral dose of crizotinib 250 mg immediate release tablet (IRT) in second intervention period. A washout period of at least 14 days was maintained between each period.
Crizotinib 250 mg Oral First, Then Crizotinib 50 mg IV Single oral dose of crizotinib 250 mg IRT in first intervention period; and single IV dose of crizotinib 50 mg in second intervention period. A washout period of at least 14 days was maintained between each period.

Participant Flow for 3 periods

Period 1:   First Intervention Period
    Crizotinib 50 mg IV First, Then Crizotinib 250 mg Oral     Crizotinib 250 mg Oral First, Then Crizotinib 50 mg IV  
STARTED     7     7  
COMPLETED     7     7  
NOT COMPLETED     0     0  

Period 2:   Washout Period (at Least 14 Days)
    Crizotinib 50 mg IV First, Then Crizotinib 250 mg Oral     Crizotinib 250 mg Oral First, Then Crizotinib 50 mg IV  
STARTED     7     7  
COMPLETED     7     7  
NOT COMPLETED     0     0  

Period 3:   Second Intervention Period
    Crizotinib 50 mg IV First, Then Crizotinib 250 mg Oral     Crizotinib 250 mg Oral First, Then Crizotinib 50 mg IV  
STARTED     7     7  
COMPLETED     7     7  
NOT COMPLETED     0     0  



  Baseline Characteristics
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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.
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Reporting Groups
  Description
Entire Study Population Includes participants randomized to receive crizotinib 50 mg IV first and crizotinib 250 mg oral first.

Baseline Measures
    Entire Study Population  
Number of Participants  
[units: participants]
  14  
Age  
[units: years]
Mean ± Standard Deviation
  35.7  ± 11.5  
Gender  
[units: participants]
 
Female     0  
Male     14  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞][dn])   [ Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hours (hrs) post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B ]

2.  Primary:   Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞])   [ Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B ]

3.  Secondary:   Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)   [ Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B ]

4.  Secondary:   Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn])   [ Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B ]

5.  Secondary:   Maximum Observed Plasma Concentration (Cmax)   [ Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B ]

6.  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 oral crizotinib dose in Treatment B ]

7.  Secondary:   Plasma Decay Half Life (t1/2)   [ Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B ]

8.  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 oral crizotinib dose in Treatment B ]

9.  Secondary:   Systemic Clearance (CL)   [ Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A ]

10.  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 oral crizotinib dose in Treatment B ]

11.  Secondary:   Volume of Distribution at Steady State (Vss)   [ Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A ]

12.  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, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B ]

13.  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 oral crizotinib dose in Treatment B ]

14.  Secondary:   Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182)   [ Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B ]

15.  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 oral crizotinib dose in Treatment B ]

16.  Secondary:   Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Last Quantifiable Concentration for Crizotinib Metabolite Ratio (MRAUClast)   [ Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B ]

17.  Secondary:   Metabolite to Parent Ratio Area Under the Curve From Time Zero to Extrapolated Infinite Time (MRAUC [0-∞])   [ Time Frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B ]

18.  Secondary:   Metabolite to Parent Ratio Maximum Observed Plasma Concentration (MRCmax)   [ Time Frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  More Information
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Certain Agreements:  
All Principal Investigators ARE employed by the organization sponsoring the study.


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: NCT01168934     History of Changes
Other Study ID Numbers: A8081010
Study First Received: July 22, 2010
Results First Received: September 12, 2011
Last Updated: October 20, 2011
Health Authority: United States: Food and Drug Administration