Relative Bioavailability Of A Crizotinib Oral Liquid Formulation To Crizotinib Formulated Capsule

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01297595
• Collaborator: (none)
• Enrollment: 22
• Location: 1
• Arm: 1
• Duration (Months): 1
• Patients Per Site Per Month: 21.6

Study Details

Study Description

Brief Summary

This study will be an open-label, randomized, 2-period, 2-treatment, 2-sequence, cross-over single-dose study employing administration of two oral formulations of crizotinib (OLF and FC) in the fasted state to healthy adult subjects. Twenty-two (22) subjects will be enrolled to obtain at least 20 evaluable subjects who complete the study. Each subject will receive two treatments (A and B) with a washout period of at least 14 days between each treatment.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Drug: crizotinib	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Phase 1, Open-Label, Single Dose, Randomized, Cross-Over Relative Bioavailability Study Comparing An Oral Liquid Formulation To A Formulated Capsule Of Crizotinib (PF 02341066) In Healthy Volunteers
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Apr 1, 2011
• Actual Study Completion Date: Apr 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: crizotinib	Drug: crizotinib; Each subject will receive 250 mg single oral doses of oral liquid formulation and formulated capsule of crizotinib separated by at least 14 days.

Outcome Measures

Primary Outcome Measures

1. Area Under the Curve From Time Zero to Infinite Time [AUC (0 - ∞)] [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hours (hrs) post crizotinib dose]

   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 - ∞).

Secondary Outcome Measures

1. Time to Reach Maximum Observed Plasma Concentration (Tmax) [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose]

2. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose]

   Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast).

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

4. Plasma Terminal Half-Life (t1/2) [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose]

   Plasma terminal half-life is the time measured for the plasma concentration to decrease by one half.

5. Apparent Oral Clearance (CL/F) [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose]

   Drug clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the plasma. Clearance obtained after oral dose (apparent oral clearance [CL/F]) is influenced by the fraction of the dose absorbed (F).

6. Apparent Volume of Distribution (Vz/F) [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose]

   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 plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.

7. Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose]

   Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast) of Crizotinib metabolite (PF-06260182).

8. Area Under the Curve From Time Zero to Infinite Time [AUC (0 - ∞)] for Crizotinib Metabolite (PF-06260182) [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose]

   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 - ∞) of crizotinib metabolite (PF-06260182).

9. Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose]

10. Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182) [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose]

11. Metabolite to Parent Ratio of Maximum Observed Plasma Concentration (MRCmax) [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose]

    Metabolite (PF-06260182) to parent (crizotinib) molar ratio of maximum observed plasma concentration (MRCmax).

12. Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Last Quantifiable Concentration (MRAUClast) [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose]

    Molar ratio of metabolite to parent area under the plasma concentration time-curve from time zero (pre-dose) to the last measured concentration (MRAUClast).

13. Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Infinite Time [MRAUC (0- ∞)] [0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose]

    Molar ratio of metabolite to parent area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0- ∞) [MRAUC (0- ∞)].

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Healthy male and/or female subjects between the ages of 18 and 55 years, inclusive. Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG or clinical laboratory tests.

• Body Mass Index (BMI) of 17.5 to 30.5 kg/m^2; and a total body weight >50 kg (110 lbs).

Exclusion Criteria:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).

• Any condition possibly affecting drug absorption (eg, gastrectomy).

• A positive urine drug screen.

• History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males (1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor) within 6 months of screening.

• Treatment with an investigational drug within 30 days (or as determined by the local requirement, whichever is longer) or 5 half-lives preceding the first dose of study medication.

• 12-lead ECG demonstrating QTc >450 msec or a QRS interval >120 msec at screening. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated two more times and the average of the three QTc or QRS values should be used to determine the subject's eligibility.

• Pregnant or nursing females; females of childbearing potential, including those with tubal ligation.

• Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication. Herbal supplements and hormonal replacement therapy must be discontinued 28 days prior to the first dose of study medication. As an exception, acetaminophen/paracetamol may be used at doses of ≤1 g/day. Limited use of non-prescription medications that are not believed to affect subject safety or the overall results of the study may be permitted on a case-by-case basis following approval by the sponsor.

• Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 56 days prior to dosing.

• History of sensitivity to heparin or heparin-induced thrombocytopenia.

• Unwilling or unable to comply with the Lifestyle Guidelines described in this protocol.

• Subjects who are investigational site staff members or subjects who are Pfizer employees directly involved in the conduct of the trial.

• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

• A positive serology for Hepatitis B or Hepatitis C.

• Subjects who currently smoke.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Bruxelles		Belgium	B-1070

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT01297595
• Other Study ID Numbers: A8081019
• First Posted: Feb 17, 2011
• Last Update Posted: Feb 16, 2012
• Last Verified: Feb 1, 2012

• Keywords provided by Pfizer: relative bioavailability; pharmacokinetics; crizotinib; oral liquid formulation; formulated capsule
• Additional relevant MeSH terms: Crizotinib

Study Results

Participant Flow

Arm/Group Title	Crizotinib 250 mg FC First, Then Crizotinib 250 mg OLF	Crizotinib 250 mg OLF First, Then Crizotinib 250 mg FC
Arm/Group Description	Single oral dose of crizotinib 250 milligram (mg) formulated capsule (FC) in first intervention period; and single oral dose of crizotinib 250 mg oral liquid formulation (OLF) in second intervention period. A washout period of at least 14 days was maintained between each crizotinib dose.	Single oral dose of crizotinib 250 mg OLF in first intervention period; and single oral dose of crizotinib 250 mg FC in second intervention period. A washout period of at least 14 days was maintained between each crizotinib dose.
Period Title: First Intervention Period
STARTED	11	11
COMPLETED	11	11
NOT COMPLETED	0	0
Period Title: First Intervention Period
STARTED	11	11
COMPLETED	11	11
NOT COMPLETED	0	0
Period Title: First Intervention Period
STARTED	11	11
COMPLETED	11	11
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Entire Study Population
Arm/Group Description	Includes participants randomized to receive crizotinib 250 mg FC first and crizotinib 250 mg OLF first.
Overall Participants	22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.0 (11.9)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	22 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Curve From Time Zero to Infinite Time [AUC (0 - ∞)]
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, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hours (hrs) post crizotinib dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) parameter analysis population included all participants randomized 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 FC	Crizotinib 250 mg OLF
Arm/Group Description	Single oral dose of crizotinib 250 mg FC [Reference] in either first intervention period or second intervention period.	Single oral dose of crizotinib 250 mg OLF [Test] in either first intervention period or second intervention period.
Measure Participants	22	22
Geometric Mean (Standard Deviation) [ng*hr/mL]	2833 (1099)	2821 (1086)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crizotinib 250 mg FC, Crizotinib 250 mg OLF
	Comments	Natural log transformed AUC (0 - ∞) of crizotinib was analyzed using a mixed effect model with sequence, period and treatment as a fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. This was an estimation study and there was no formal statistical hypothesis.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Adjusted Means
	Estimated Value	99.58
	Confidence Interval	(2-Sided) 90%; 91.08 to 108.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized 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 FC	Crizotinib 250 mg OLF
Arm/Group Description	Single oral dose of crizotinib 250 mg FC [Reference] in either first intervention period or second intervention period.	Single oral dose of crizotinib 250 mg OLF [Test] in either first intervention period or second intervention period.
Measure Participants	22	22
Median (Full Range) [hr]	5.00	5.00

3. Secondary Outcome

Title	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
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, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized 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 FC	Crizotinib 250 mg OLF
Arm/Group Description	Single oral dose of crizotinib 250 mg FC [Reference] in either first intervention period or second intervention period.	Single oral dose of crizotinib 250 mg OLF [Test] in either first intervention period or second intervention period.
Measure Participants	22	22
Geometric Mean (Standard Deviation) [ng*hr/mL]	2696 (1073)	2679 (1069)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crizotinib 250 mg FC, Crizotinib 250 mg OLF
	Comments	Natural log transformed AUClast of crizotinib was analyzed using a mixed effect model with sequence, period and treatment as a fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. This was an estimation study and there was no formal statistical hypothesis.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Adjusted Means
	Estimated Value	99.35
	Confidence Interval	(2-Sided) 90%; 90.51 to 109.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
Time Frame	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized 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 FC	Crizotinib 250 mg OLF
Arm/Group Description	Single oral dose of crizotinib 250 mg FC [Reference] in either first intervention period or second intervention period.	Single oral dose of crizotinib 250 mg OLF [Test] in either first intervention period or second intervention period.
Measure Participants	22	22
Geometric Mean (Standard Deviation) [ng/mL]	121.0 (38.9)	117.2 (36.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Crizotinib 250 mg FC, Crizotinib 250 mg OLF
	Comments	Natural log transformed Cmax of crizotinib was analyzed using a mixed effect model with sequence, period and treatment as a fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios. This was an estimation study and there was no formal statistical hypothesis.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio of Adjusted Means
	Estimated Value	96.84
	Confidence Interval	(2-Sided) 90%; 88.22 to 106.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Plasma Terminal Half-Life (t1/2)
Description	Plasma terminal half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized 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 FC	Crizotinib 250 mg OLF
Arm/Group Description	Single oral dose of crizotinib 250 mg FC [Reference] in either first intervention period or second intervention period.	Single oral dose of crizotinib 250 mg OLF [Test] in either first intervention period or second intervention period.
Measure Participants	22	22
Mean (Standard Deviation) [hr]	35.58 (6.12)	36.35 (5.64)

6. Secondary Outcome

Title	Apparent Oral Clearance (CL/F)
Description	Drug clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the plasma. Clearance obtained after oral dose (apparent oral clearance [CL/F]) is influenced by the fraction of the dose absorbed (F).
Time Frame	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized 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 FC	Crizotinib 250 mg OLF
Arm/Group Description	Single oral dose of crizotinib 250 mg FC [Reference] in either first intervention period or second intervention period.	Single oral dose of crizotinib 250 mg OLF [Test] in either first intervention period or second intervention period.
Measure Participants	22	22
Geometric Mean (Standard Deviation) [Liter/hour (L/hr)]	88.21 (30.17)	88.61 (28.96)

7. Secondary Outcome

Title	Apparent Volume of Distribution (Vz/F)
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 plasma 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, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized 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 FC	Crizotinib 250 mg OLF
Arm/Group Description	Single oral dose of crizotinib 250 mg FC [Reference] in either first intervention period or second intervention period.	Single oral dose of crizotinib 250 mg OLF [Test] in either first intervention period or second intervention period.
Measure Participants	22	22
Geometric Mean (Standard Deviation) [Liter]	4473 (2089)	4593 (2108)

8. Secondary Outcome

Title	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182)
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, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized 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 FC	Crizotinib 250 mg OLF
Arm/Group Description	Single oral dose of crizotinib 250 mg FC [Reference] in either first intervention period or second intervention period.	Single oral dose of crizotinib 250 mg OLF [Test] in either first intervention period or second intervention period.
Measure Participants	22	22
Geometric Mean (Standard Deviation) [ng*hr/mL]	429.5 (242.3)	439.1 (271.5)

9. Secondary Outcome

Title	Area Under the Curve From Time Zero to Infinite Time [AUC (0 - ∞)] for Crizotinib Metabolite (PF-06260182)
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 - ∞) of crizotinib metabolite (PF-06260182).
Time Frame	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. 'N' = Number of participants contributing to the mean.

Arm/Group Title	Crizotinib 250 mg FC	Crizotinib 250 mg OLF
Arm/Group Description	Single oral dose of crizotinib 250 mg FC [Reference] in either first intervention period or second intervention period.	Single oral dose of crizotinib 250 mg OLF [Test] in either first intervention period or second intervention period.
Measure Participants	21	22
Geometric Mean (Standard Deviation) [ng*hr/mL]	454.4 (242.1)	446.7 (273.1)

10. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182)
Time Frame	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized 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 FC	Crizotinib 250 mg OLF
Arm/Group Description	Single oral dose of crizotinib 250 mg FC [Reference] in either first intervention period or second intervention period.	Single oral dose of crizotinib 250 mg OLF [Test] in either first intervention period or second intervention period.
Measure Participants	22	22
Geometric Mean (Standard Deviation) [ng/mL]	30.98 (10.39)	32.56 (10.75)

11. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182)
Time Frame	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized 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 FC	Crizotinib 250 mg OLF
Arm/Group Description	Single oral dose of crizotinib 250 mg FC [Reference] in either first intervention period or second intervention period.	Single oral dose of crizotinib 250 mg OLF [Test] in either first intervention period or second intervention period.
Measure Participants	22	22
Median (Full Range) [hr]	5.00	5.00

12. Secondary Outcome

Title	Metabolite to Parent Ratio of Maximum Observed Plasma Concentration (MRCmax)
Description	Metabolite (PF-06260182) to parent (crizotinib) molar ratio of maximum observed plasma concentration (MRCmax).
Time Frame	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized 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 FC	Crizotinib 250 mg OLF
Arm/Group Description	Single oral dose of crizotinib 250 mg FC [Reference] in either first intervention period or second intervention period.	Single oral dose of crizotinib 250 mg OLF [Test] in either first intervention period or second intervention period.
Measure Participants	22	22
Geometric Mean (Standard Deviation) [Ratio]	0.2482 (0.0349)	0.2694 (0.0532)

13. Secondary Outcome

Title	Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Last Quantifiable Concentration (MRAUClast)
Description	Molar ratio of metabolite to parent area under the plasma concentration time-curve from time zero (pre-dose) to the last measured concentration (MRAUClast).
Time Frame	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized 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 FC	Crizotinib 250 mg OLF
Arm/Group Description	Single oral dose of crizotinib 250 mg FC [Reference] in either first intervention period or second intervention period.	Single oral dose of crizotinib 250 mg OLF [Test] in either first intervention period or second intervention period.
Measure Participants	22	22
Geometric Mean (Standard Deviation) [Ratio]	0.1546 (0.0275)	0.1589 (0.0274)

14. Secondary Outcome

Title	Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Infinite Time [MRAUC (0- ∞)]
Description	Molar ratio of metabolite to parent area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0- ∞) [MRAUC (0- ∞)].
Time Frame	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, 96 and 144 hrs post crizotinib dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all participants randomized and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. 'N' = Number of participants contributing to the mean.

Arm/Group Title	Crizotinib 250 mg FC	Crizotinib 250 mg OLF
Arm/Group Description	Single oral dose of crizotinib 250 mg FC [Reference] in either first intervention period or second intervention period.	Single oral dose of crizotinib 250 mg OLF [Test] in either first intervention period or second intervention period.
Measure Participants	21	22
Geometric Mean (Standard Deviation) [Ratio]	0.1514 (0.0254)	0.1535 (0.0259)

Adverse Events

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 FC		Crizotinib 250 mg OLF
Arm/Group Description	Single oral dose of crizotinib 250 mg FC [Reference] in either first intervention period or second intervention period.		Single oral dose of crizotinib 250 mg OLF [Test] in either first intervention period or second intervention period.
All Cause Mortality
	Crizotinib 250 mg FC		Crizotinib 250 mg OLF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Crizotinib 250 mg FC		Crizotinib 250 mg OLF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/22 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Crizotinib 250 mg FC		Crizotinib 250 mg OLF
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/22 (77.3%)		17/22 (77.3%)
Ear and labyrinth disorders
Ear pain	0/22 (0%)		1/22 (4.5%)
Gastrointestinal disorders
Abdominal distension	1/22 (4.5%)		0/22 (0%)
Abdominal pain	4/22 (18.2%)		7/22 (31.8%)
Abdominal pain upper	1/22 (4.5%)		0/22 (0%)
Diarrhoea	9/22 (40.9%)		10/22 (45.5%)
Dyspepsia	0/22 (0%)		2/22 (9.1%)
Eructation	0/22 (0%)		2/22 (9.1%)
Faeces discoloured	1/22 (4.5%)		0/22 (0%)
Flatulence	1/22 (4.5%)		0/22 (0%)
Gastrointestinal sounds abnormal	2/22 (9.1%)		1/22 (4.5%)
Nausea	6/22 (27.3%)		6/22 (27.3%)
General disorders
Fatigue	1/22 (4.5%)		1/22 (4.5%)
Feeling cold	0/22 (0%)		1/22 (4.5%)
Influenza like illness	0/22 (0%)		1/22 (4.5%)
Infections and infestations
Gastroenteritis	1/22 (4.5%)		0/22 (0%)
Nasopharyngitis	1/22 (4.5%)		1/22 (4.5%)
Nervous system disorders
Dizziness	2/22 (9.1%)		0/22 (0%)
Dizziness postural	1/22 (4.5%)		0/22 (0%)
Headache	5/22 (22.7%)		7/22 (31.8%)
Hypersomnia	0/22 (0%)		1/22 (4.5%)
Somnolence	0/22 (0%)		1/22 (4.5%)
Psychiatric disorders
Abnormal dreams	1/22 (4.5%)		1/22 (4.5%)
Initial insomnia	0/22 (0%)		1/22 (4.5%)
Insomnia	1/22 (4.5%)		0/22 (0%)
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	1/22 (4.5%)		0/22 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

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.