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

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Pfizer

ClinicalTrials.gov Identifier:

NCT01147055

First received: June 16, 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: Non-Randomized; Endpoint Classification: Pharmacokinetics Study; Intervention Model: Crossover Assignment; Masking: Open Label
Condition:	Healthy
Interventions:	Drug: crizotinib Drug: rifampin

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	Single oral dose of crizotinib 250 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 250 mg + Rifampin 600 mg	Single oral dose of rifampin 600 mg tablet in fasted state from Day 1 to Day 14. A single oral dose of crizotinib 250 mg IRTs was administered on Day 9 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 250 mg	Crizotinib 250 mg + Rifampin 600 mg
STARTED	15	0
COMPLETED	14	0
NOT COMPLETED	1	0
Lost to Follow-up	1	0

Period 2: Washout Period (at Least 14 Days)

	Crizotinib 250 mg	Crizotinib 250 mg + Rifampin 600 mg
STARTED	14	0
COMPLETED	14	0
NOT COMPLETED	0	0

Period 3: Second Intervention Period

	Crizotinib 250 mg	Crizotinib 250 mg + Rifampin 600 mg
STARTED	0	14
COMPLETED	0	14
NOT COMPLETED	0	0

Baseline Characteristics

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Reporting Groups

	Description
Entire Study Population	Includes participants randomized to receive crizotinib 250 mg IRT first and then crizotinib 250 mg + rifampin 600 mg.

Baseline Measures

	Entire Study Population
Number of Participants [units: participants]	15
Age [units: years] Mean ± Standard Deviation	38.9 ± 8.5
Gender [units: participants]
Female	1
Male	14

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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2 ]

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

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

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

Hide Outcome Measure 4

Measure Type	Secondary
Measure Title	Time to Reach Maximum Observed Plasma Concentration (Tmax)
Measure Description	No text entered.
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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
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.
The PK parameter analysis population included all enrolled 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 250 mg	Single oral dose of crizotinib 250 mg IRT in first intervention period [Treatment A (Reference)].
Crizotinib 250 mg + Rifampin 600 mg	Single oral dose of rifampin 600 mg tablet in the fasted state from Day 1 to Day 14 and single oral dose of crizotinib 250 mg IRTs on Day 9 in second intervention period [Treatment B (Test)].

Measured Values

	Crizotinib 250 mg	Crizotinib 250 mg + Rifampin 600 mg
Number of Participants Analyzed [units: participants]	15	14
Time to Reach Maximum Observed Plasma Concentration (Tmax) [units: hr] Median ( Full Range )	5.0 ( 4.0 to 6.0 )	3.0 ( 2.0 to 5.0 )

No statistical analysis provided for Time to Reach Maximum Observed Plasma Concentration (Tmax)

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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2 ]

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

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

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, 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2 ]

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

Show Outcome Measure 9

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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2 ]

Show Outcome Measure 10

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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2 ]

Show Outcome Measure 11

12. Secondary:

Metabolite to Parent Ratio Area Under the Curve From Time Zero to Last Quantifiable Concentration (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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2 ]

Show Outcome Measure 12

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

Show Outcome Measure 13

14. Secondary:

Metabolite to Parent Ratio 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2 ]

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:

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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

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:	NCT01147055 History of Changes
Other Study ID Numbers:	A8081016
Study First Received:	June 16, 2010
Results First Received:	September 12, 2011
Last Updated:	October 20, 2011
Health Authority:	United States: Food and Drug Administration

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