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

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ClinicalTrials.gov Identifier: NCT01147055
Recruitment Status : Completed
First Posted : June 22, 2010
Results First Posted : October 19, 2011
Last Update Posted : October 24, 2011
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Crossover Assignment;   Masking: None (Open Label)
Condition Healthy
Interventions Drug: crizotinib
Drug: rifampin
Enrollment 15
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Hide Arm/Group Description 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. 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.
Period Title: First Intervention Period
Started 15 0
Completed 14 0
Not Completed 1 0
Reason Not Completed
Lost to Follow-up             1             0
Period Title: Washout Period (at Least 14 Days)
Started 14 0
Completed 14 0
Not Completed 0 0
Period Title: Second Intervention Period
Started 0 14
Completed 0 14
Not Completed 0 0
Arm/Group Title Entire Study Population
Hide Arm/Group Description Includes participants randomized to receive crizotinib 250 mg IRT first and then crizotinib 250 mg + rifampin 600 mg.
Overall Number of Baseline Participants 15
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants
38.9  (8.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants
Female
1
   6.7%
Male
14
  93.3%
1.Primary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
Hide 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, 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
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (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.
Arm/Group Title Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Hide Arm/Group Description:
Single oral dose of crizotinib 250 mg IRT in first intervention period [Treatment A (Reference)].
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)].
Overall Number of Participants Analyzed 15 14
Geometric Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
2192.00  (616.59) 397.20  (106.12)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib 250 mg, Crizotinib 250 mg + Rifampin 600 mg
Comments Natural log transformed AUC (0-∞) of crizotinib was analyzed using a mixed effect model with treatment as a fixed effect and participant as a random effect. The adjusted mean differences and 90% confidence intervals (CIs) for the differences was exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Adjusted Means
Estimated Value 18.21
Confidence Interval (2-Sided) 90%
16.14 to 20.54
Estimation Comments [Not Specified]
2.Primary Outcome
Title Maximum Observed Plasma Concentration (Cmax)
Hide Description [Not Specified]
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 Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Hide Arm/Group Description:
Single oral dose of crizotinib 250 mg IRT in first intervention period [Treatment A (Reference)].
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)].
Overall Number of Participants Analyzed 15 14
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
102.10  (35.64) 32.06  (11.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib 250 mg, Crizotinib 250 mg + Rifampin 600 mg
Comments Natural log transformed Cmax of crizotinib was analyzed using a mixed effect model with treatment as a fixed effect and participant as a random effect. The adjusted mean differences and 90% CIs for the differences was exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Adjusted Means
Estimated Value 31.49
Confidence Interval (2-Sided) 90%
26.43 to 37.51
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Hide Description Area under the plasma concentration time-curve from zero (pre-dose) to the last measured 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Hide Arm/Group Description:
Single oral dose of crizotinib 250 mg IRT in first intervention period [Treatment A (Reference)].
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)].
Overall Number of Participants Analyzed 15 14
Geometric Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
2103.00  (620.52) 368.60  (101.93)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib 250 mg, Crizotinib 250 mg + Rifampin 600 mg
Comments Natural log transformed AUClast of crizotinib was analyzed using a mixed effect model with treatment as a fixed effect and participant as a random effect. The adjusted mean differences and 90% CIs for the differences was exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Adjusted Means
Estimated Value 17.60
Confidence Interval (2-Sided) 90%
15.48 to 20.02
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax)
Hide Description [Not Specified]
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 Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Hide Arm/Group Description:
Single oral dose of crizotinib 250 mg IRT in first intervention period [Treatment A (Reference)].
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)].
Overall Number of Participants Analyzed 15 14
Median (Full Range)
Unit of Measure: hr
5.0
(4.0 to 6.0)
3.0
(2.0 to 5.0)
5.Secondary Outcome
Title Plasma Decay Half-Life (t1/2)
Hide Description Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
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 Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Hide Arm/Group Description:
Single oral dose of crizotinib 250 mg IRT in first intervention period [Treatment A (Reference)].
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)].
Overall Number of Participants Analyzed 15 14
Mean (Standard Deviation)
Unit of Measure: hr
33.07  (6.96) 48.23  (5.62)
6.Secondary Outcome
Title Apparent Oral Clearance (CL/F)
Hide Description Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose CL/F is influenced by the fraction of the dose 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 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 Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Hide Arm/Group Description:
Single oral dose of crizotinib 250 mg IRT in first intervention period [Treatment A (Reference)].
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)].
Overall Number of Participants Analyzed 15 14
Geometric Mean (Standard Deviation)
Unit of Measure: L/hr
118.80  (37.39) 648.60  (164.95)
7.Secondary Outcome
Title Apparent Volume of Distribution (Vz/F)
Hide 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 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 Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Hide Arm/Group Description:
Single oral dose of crizotinib 250 mg IRT in first intervention period [Treatment A (Reference)].
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)].
Overall Number of Participants Analyzed 15 14
Geometric Mean (Standard Deviation)
Unit of Measure: L
5940.0  (3242.9) 45720.0  (15766.0)
8.Secondary Outcome
Title Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182)
Hide Description Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast) of 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Hide Arm/Group Description:
Single oral dose of crizotinib 250 mg IRT in first intervention period [Treatment A (Reference)].
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)].
Overall Number of Participants Analyzed 15 14
Geometric Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
369.50  (119.58) 20.28  (8.19)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib 250 mg, Crizotinib 250 mg + Rifampin 600 mg
Comments Natural log transformed AUClast of PF-06260182 was analyzed using a mixed effect model with treatment as a fixed effect and participant as a random effect. The adjusted mean differences and 90% CIs for the differences was exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Adjusted Means
Estimated Value 5.49
Confidence Interval (2-Sided) 90%
4.64 to 6.49
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for Crizotinib Metabolite (PF-06260182)
Hide Description AUC (0 - ∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞) of crizotinib metabolite (PF-06260182). It is obtained from AUC (0 - t) plus AUC (t - ∞).
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 Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Hide Arm/Group Description:
Single oral dose of crizotinib 250 mg IRT in first intervention period [Treatment A (Reference)].
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)].
Overall Number of Participants Analyzed 15 14
Geometric Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
378.60  (120.38) 21.78  (8.98)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib 250 mg, Crizotinib 250 mg + Rifampin 600 mg
Comments Natural log transformed AUC (0 - ∞) of PF-06260182 was analyzed using a mixed effect model with treatment as a fixed effect and participant as a random effect. The adjusted mean differences and 90% CIs for the differences was exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Adjusted Means
Estimated Value 5.75
Confidence Interval (2-Sided) 90%
4.86 to 6.81
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182)
Hide Description [Not Specified]
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 Data
Hide Analysis Population Description
The PK parameter analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
Arm/Group Title Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Hide Arm/Group Description:
Single oral dose of crizotinib 250 mg IRT in first intervention period [Treatment A (Reference)].
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)].
Overall Number of Participants Analyzed 15 14
Median (Full Range)
Unit of Measure: hr
5.0
(4.0 to 8.0)
5.0
(2.0 to 6.0)
11.Secondary Outcome
Title Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182)
Hide Description [Not Specified]
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 Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Hide Arm/Group Description:
Single oral dose of crizotinib 250 mg IRT in first intervention period [Treatment A (Reference)].
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)].
Overall Number of Participants Analyzed 15 14
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
29.88  (10.22) 3.29  (1.23)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Crizotinib 250 mg, Crizotinib 250 mg + Rifampin 600 mg
Comments Natural log transformed Cmax of PF-06260182 was analyzed using a mixed effect model with treatment as a fixed effect and participant as a random effect. The adjusted mean differences and 90% CIs for the differences was exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of Adjusted Means
Estimated Value 11.01
Confidence Interval (2-Sided) 90%
9.02 to 13.45
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Metabolite to Parent Ratio Area Under the Curve From Time Zero to Last Quantifiable Concentration (MRAUClast)
Hide Description Molar ratio of metabolite to parent area under the plasma concentration time-curve from zero (pre-dose) to the last measured 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Hide Arm/Group Description:
Single oral dose of crizotinib 250 mg IRT in first intervention period [Treatment A (Reference)].
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)].
Overall Number of Participants Analyzed 15 14
Geometric Mean (Standard Deviation)
Unit of Measure: Ratio
0.1703  (0.0264) 0.0533  (0.0112)
13.Secondary Outcome
Title Metabolite to Parent Ratio Area Under the Curve From Time Zero to Extrapolated Infinite Time [MRAUC (0 - ∞)]
Hide Description Molar ratio of metabolite to parent 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Hide Arm/Group Description:
Single oral dose of crizotinib 250 mg IRT in first intervention period [Treatment A (Reference)].
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)].
Overall Number of Participants Analyzed 15 14
Geometric Mean (Standard Deviation)
Unit of Measure: Ratio
0.1676  (0.0271) 0.0532  (0.0113)
14.Secondary Outcome
Title Metabolite to Parent Ratio Maximum Observed Plasma Concentration (MRCmax)
Hide Description Metabolite to parent molar 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Hide Arm/Group Description:
Single oral dose of crizotinib 250 mg IRT in first intervention period [Treatment A (Reference)].
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)].
Overall Number of Participants Analyzed 15 14
Geometric Mean (Standard Deviation)
Unit of Measure: Ratio
0.2839  (0.0711) 0.0996  (0.0382)
Time Frame [Not Specified]
Adverse Event Reporting Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Hide Arm/Group Description Single oral dose of crizotinib 250 mg IRT in first intervention period [Treatment A (Reference)]. 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)].
All-Cause Mortality
Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/15 (0.00%)   0/14 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Crizotinib 250 mg Crizotinib 250 mg + Rifampin 600 mg
Affected / at Risk (%) Affected / at Risk (%)
Total   3/15 (20.00%)   3/14 (21.43%) 
Eye disorders     
Eye swelling * 1  0/15 (0.00%)  0/14 (0.00%) 
Gastrointestinal disorders     
Constipation * 1  0/15 (0.00%)  2/14 (14.29%) 
Diarrhoea * 1  2/15 (13.33%)  1/14 (7.14%) 
Nausea * 1  1/15 (6.67%)  0/14 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain * 1  1/15 (6.67%)  0/14 (0.00%) 
Nervous system disorders     
Headache * 1  0/15 (0.00%)  0/14 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Epistaxis * 1  1/15 (6.67%)  0/14 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (13.0)
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.
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.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01147055     History of Changes
Other Study ID Numbers: A8081016
First Submitted: June 16, 2010
First Posted: June 22, 2010
Results First Submitted: September 12, 2011
Results First Posted: October 19, 2011
Last Update Posted: October 24, 2011