Estimation Of Effect Of Ketoconazole On Pharmacokinetics Of Crizotinib In Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01149785
First received: June 21, 2010
Last updated: October 20, 2011
Last verified: October 2011
Results First Received: September 12, 2011  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Crossover Assignment;   Masking: Open Label
Condition: Healthy
Interventions: Drug: crizotinib
Drug: ketoconazole

  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
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Reporting Groups
  Description
Crizotinib 150 mg Single oral dose of crizotinib 150 milligram (mg) immediate-release tablet (IRT) on Day 1 in first intervention period. A washout period of at least 14 days was maintained between each period.
Crizotinib 150 mg + Ketoconazole 200 mg BID Ketoconazole 200 mg tablet twice daily (BID), orally in fasted state from Day 1 to Day 16 and single oral dose of crizotinib 150 mg IRT on Day 4 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
    Crizotinib 150 mg     Crizotinib 150 mg + Ketoconazole 200 mg BID  
STARTED     15     0  
COMPLETED     15     0  
NOT COMPLETED     0     0  

Period 2:   Washout Period of at Least 14 Days
    Crizotinib 150 mg     Crizotinib 150 mg + Ketoconazole 200 mg BID  
STARTED     15     0  
COMPLETED     15     0  
NOT COMPLETED     0     0  

Period 3:   Second Intervention
    Crizotinib 150 mg     Crizotinib 150 mg + Ketoconazole 200 mg BID  
STARTED     0     15  
COMPLETED     0     15  
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 150 mg IRT first and then Crizotinib 150 mg + Ketoconazole 200 mg BID

Baseline Measures
    Entire Study Population  
Number of Participants  
[units: participants]
  15  
Age  
[units: years]
Mean ± Standard Deviation
  36.5  ± 7.6  
Gender  
[units: participants]
 
Female     0  
Male     15  



  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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ]

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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ]

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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ]

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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ]

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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ]

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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ]

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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ]

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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ]

10.  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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ]

11.  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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ]

12.  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, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ]

13.  Secondary:   Metabolite to Parent Ratio of 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 crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ]

14.  Secondary:   Metabolite to Parent Ratio of Maximum Observed Plasma Concentration (MRCmax)   [ Time Frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 ]


  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:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


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: NCT01149785     History of Changes
Other Study ID Numbers: A8081015
Study First Received: June 21, 2010
Results First Received: September 12, 2011
Last Updated: October 20, 2011
Health Authority: United States: Food and Drug Administration