Bioequivalence And Food Effect Study Comparing The Commer... | NCT01154218

Label	Type	Description	Intervention Names
1	Experimental	All subjects will receive four treatments in one of the indicated orders: A-B-C-D, B-D-A-C, C-A-D-B, D-C-B-A	Drug: crizotinib

Name	Type	Description	Arm Group Labels	Other Names
crizotinib	Drug	Treatment A (Reference 1): a 250 mg single dose of crizotinib administered in a fasted state as 1 × 50-mg IRT and 2 × 100-mg IRTs. Treatment B (Reference 2): a 250 mg single dose of crizotinib administered in a fasted state as 1 × 50-mg PIC and 2 × 100 mg PICs. Treatment C (Test for BE, Reference for Food Effect): a 250 mg single dose of crizotinib administered in a fasted state as 1 × 250-mg CIC. Treatment D (Test High Fat): a 250 mg single dose of crizotinib administered with a high-fat meal as 1 × 250-mg CIC

Measure	Description	Time Frame
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞])	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-∞).	0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hours (hrs) post crizotinib dose
Maximum Observed Plasma Concentration (Cmax)		0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose

Measure	Description	Time Frame
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast).	0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose
Time to Reach Maximum Observed Plasma Concentration (Tmax)

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pfizer Investigational Site		Brussels		B-1070	Belgium

Label	URL
To obtain contact information for a study center near you, click here.	View source

ID	Title	Description
FG000	Crizotinib 250 mg IRT Fasted, PIC Fasted, CIC Fasted, CIC Fed	Single oral dose of crizotinib 250 milligram (mg) immediate release tablet (IRT) in fasted state in first intervention period; followed by single oral dose of crizotinib 250 mg powder in capsule (PIC) in fasted state in second intervention period; followed by single oral dose of crizotinib 250 mg commercial image capsule (CIC) in fasted state in third intervention period; and single oral dose of crizotinib 250 mg CIC in fed state in fourth intervention period. A washout period of at least 14 days was maintained between each period.

ID	Title	Description
BG000	Entire Study Population	Includes participants randomized to receive any treatment (crizotinib 250 mg IRT fasted first, crizotinib 250 mg PIC fasted first, crizotinib 250 mg CIC fasted first and crizotinib 250 mg CIC fed).

Units	Counts
Participants	BG00036

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞])

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-∞).

Pharmacokinetic (PK) parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.

Posted

Geometric Mean

Standard Deviation

ng*hr/mL

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

ID	Title	Description
OG000	Crizotinib IRT Fasted	Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period.
OG001	Crizotinib PIC Fasted	Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period.
OG002	Crizotinib CIC Fasted	Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period.
OG003	Crizotinib CIC Fed	Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period.

Units	Counts
Participants	OG00035 OG00135 OG00235 OG003

Title

Denominators

Categories

Title	Measurements
	OG0002890.0± 1021.8 OG0012665.0± 1190.4 OG0022887.0± 1109.6 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002	Natural log transformed AUC (0-∞) of crizotinib was analyzed using a mixed effect model with sequence, period and treatment as 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.					Ratio of Adjusted Means	99.56			2-Sided	90	91.49	108.33				No	Superiority or Other

Secondary

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)

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

PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.

Posted

Geometric Mean

Standard Deviation

ng*hr/mL

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

ID	Title	Description
OG000	Crizotinib IRT Fasted	Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period.
OG001	Crizotinib PIC Fasted	Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period.
OG002	Crizotinib CIC Fasted	Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period.
OG003	Crizotinib CIC Fed

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax)

PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.

Posted

Median

Full Range

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

ID	Title	Description
OG000	Crizotinib IRT Fasted	Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period.
OG001	Crizotinib PIC Fasted	Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period.
OG002	Crizotinib CIC Fasted	Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period.
OG003	Crizotinib CIC Fed	Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period.

Secondary

Plasma Decay Half Life (t1/2)

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

PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.

Posted

Mean

Standard Deviation

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

ID	Title	Description
OG000	Crizotinib IRT Fasted	Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period.
OG001	Crizotinib PIC Fasted	Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period.
OG002	Crizotinib CIC Fasted	Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period.
OG003	Crizotinib CIC Fed

Primary

Maximum Observed Plasma Concentration (Cmax)

PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.

Posted

Geometric Mean

Standard Deviation

ng/mL

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

ID	Title	Description
OG000	Crizotinib IRT Fasted	Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period.
OG001	Crizotinib PIC Fasted	Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period.
OG002	Crizotinib CIC Fasted	Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period.
OG003	Crizotinib CIC Fed	Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period.

Secondary

Apparent Oral Clearance (CL/F)

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

PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.

Posted

Geometric Mean

Standard Deviation

L/hr

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

ID	Title	Description
OG000	Crizotinib IRT Fasted	Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period.
OG001	Crizotinib PIC Fasted	Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period.
OG002	Crizotinib CIC Fasted	Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period.
OG003

Secondary

Apparent Volume of Distribution (Vz/F)

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.

PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.

Posted

Geometric Mean

Standard Deviation

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

ID	Title	Description
OG000	Crizotinib IRT Fasted	Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period.
OG001	Crizotinib PIC Fasted	Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period.
OG002	Crizotinib CIC Fasted	Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period.

Secondary

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182)

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

PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.

Posted

Geometric Mean

Standard Deviation

ng*hr/mL

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

ID	Title	Description
OG000	Crizotinib IRT Fasted	Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period.
OG001	Crizotinib PIC Fasted	Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period.
OG002	Crizotinib CIC Fasted	Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period.

Secondary

Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) for Crizotinib Metabolite (PF-06260182)

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-∞).

PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Here, the 'N = 35' is signifying those participants who were evaluable for this measure at the specified time point for crizotinib CIC fed arm group.

Posted

Geometric Mean

Standard Deviation

ng*hr/mL

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

ID	Title	Description
OG000	Crizotinib IRT Fasted	Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period.
OG001	Crizotinib PIC Fasted	Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period.
OG002	Crizotinib CIC Fasted	Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period.

Secondary

Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182)

PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.

Posted

Geometric Mean

Standard Deviation

ng/mL

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

ID	Title	Description
OG000	Crizotinib IRT Fasted	Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period.
OG001	Crizotinib PIC Fasted	Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period.
OG002	Crizotinib CIC Fasted	Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period.
OG003	Crizotinib CIC Fed	Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period.

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182)

PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.

Posted

Median

Full Range

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

ID	Title	Description
OG000	Crizotinib IRT Fasted	Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period.
OG001	Crizotinib PIC Fasted	Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period.
OG002	Crizotinib CIC Fasted	Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period.
OG003	Crizotinib CIC Fed	Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period.

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal discomfort	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected36 at risk EG0011 affected36 at risk EG0021 affected36 at risk EG0030 affected36 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected36 at risk EG0011 affected36 at risk EG0020 affected36 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected36 at risk EG0011 affected36 at risk EG0020 affected36 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected36 at risk EG0011 affected36 at risk EG0021 affected36 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected36 at risk EG0011 affected36 at risk EG0020 affected36 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0009 affected36 at risk EG00113 affected36 at risk EG00213 affected36 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected36 at risk EG0010 affected36 at risk EG0020 affected36 at risk EG003
Epigastric discomfort	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0002 affected36 at risk EG0011 affected36 at risk EG0022 affected36 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected36 at risk EG0011 affected36 at risk EG0020 affected36 at risk EG003
Gastrointestinal sounds abnormal	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected36 at risk EG0010 affected36 at risk EG0021 affected36 at risk EG003
Gingivitis	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected36 at risk EG0010 affected36 at risk EG0021 affected36 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0005 affected36 at risk EG00110 affected36 at risk EG0022 affected36 at risk EG003
Salivary hypersecretion	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected36 at risk EG0011 affected36 at risk EG0021 affected36 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected36 at risk EG0012 affected36 at risk EG0020 affected36 at risk EG003
Fatigue	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0003 affected36 at risk EG0015 affected36 at risk EG0022 affected36 at risk EG003
Feeling cold	General disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected36 at risk EG0011 affected36 at risk EG0020 affected36 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0002 affected36 at risk EG0013 affected36 at risk EG0020 affected36 at risk EG003
Tooth abscess	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected36 at risk EG0010 affected36 at risk EG0020 affected36 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 13.1	Non-systematic Assessment	EG0000 affected36 at risk EG0010 affected36 at risk EG0020 affected36 at risk EG003
Joint sprain	Injury, poisoning and procedural complications	MedDRA 13.1	Non-systematic Assessment	EG0001 affected36 at risk EG0011 affected36 at risk EG0020 affected36 at risk EG003
Hepatic enzyme increased	Investigations	MedDRA 13.1	Non-systematic Assessment	EG0001 affected36 at risk EG0010 affected36 at risk EG0020 affected36 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected36 at risk EG0011 affected36 at risk EG0020 affected36 at risk EG003
Dizziness	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected36 at risk EG0011 affected36 at risk EG0020 affected36 at risk EG003
Dizziness postural	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected36 at risk EG0011 affected36 at risk EG0020 affected36 at risk EG003
Headache	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0004 affected36 at risk EG0015 affected36 at risk EG0024 affected36 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected36 at risk EG0011 affected36 at risk EG0021 affected36 at risk EG003
Somnolence	Nervous system disorders	MedDRA 13.1	Non-systematic Assessment	EG0001 affected36 at risk EG0011 affected36 at risk EG0021 affected36 at risk EG003
Hot flush	Vascular disorders	MedDRA 13.1	Non-systematic Assessment	EG0000 affected36 at risk EG0010 affected36 at risk EG0020 affected36 at risk EG003

ID	Term
D010880	Piperidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D000631	Aminopyridines
D011725	Pyridines

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Crizotinib IRT Fasted	Single oral dose of crizotinib 250 mg IRT (Treatment A [Reference 1]) in fasted state in any intervention period.	36	21	36
EG001	Crizotinib PIC Fasted	Single oral dose of crizotinib 250 mg PIC (Treatment B [Reference 2]) in fasted state in any intervention period.	36	24	36
EG002	Crizotinib CIC Fasted	Single oral dose of crizotinib 250 mg CIC (Treatment C [Test for bioequivalence (BE), Reference for Food effect]) in fasted state in any intervention period.	36	20	36
EG003	Crizotinib CIC Fed	Single oral dose of crizotinib 250 mg CIC (Treatment D [Test High Fat]) in fed state in any intervention period.	36	21	36