Trial Outcomes & Findings for A Study In Japanese Healthy Male Volunteers To Investigate The Safety, Tolerability And Pharmacokinetics Of PF-02341066 (NCT NCT01250730)

NCT ID: NCT01250730

Last Updated: 2011-11-29

Results Overview

AUC(0-inf) of crizotinib is estimated from the crizotinib concentration. It is obtained from AUClast plus (Clast/kel). AUClast = area under the plasma concentration-time curve from zero time until the last measurable concentration. Clast = the last quantifiable concentration. Kel = terminal phase elimination rate constant.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 18 participants
• Primary outcome timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose
• Results posted on: 2011-11-29

Participant Flow

Twelve healthy subjects were assigned to open-label crizotinib treatment in either the 150 mg cohort (6 subjects) or 250 mg cohort (6 subjects). After the completion of assessment of safety at both 150 mg and 250 mg cohorts, the 400 mg cohort, the highest dose level in this study, was started.

Participant milestones

Measure	Crizotinib 150 mg A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Overall Study STARTED	6	6	6
Overall Study COMPLETED	6	6	6
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study In Japanese Healthy Male Volunteers To Investigate The Safety, Tolerability And Pharmacokinetics Of PF-02341066

Baseline characteristics by cohort

Measure	Crizotinib 150 mg n=6 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.	Total n=18 Participants Total of all reporting groups
Sex: Female, Male Male	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	18 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

AUC(0-inf) of crizotinib is estimated from the crizotinib concentration. It is obtained from AUClast plus (Clast/kel).

AUClast = area under the plasma concentration-time curve from zero time until the last measurable concentration.

Clast = the last quantifiable concentration. Kel = terminal phase elimination rate constant.

Outcome measures

Measure	Crizotinib 150 mg n=6 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time [AUC(0-inf)] of Crizotinib	1423 ng*hr/mL Standard Deviation 471.52	3806 ng*hr/mL Standard Deviation 1313.2	6569 ng*hr/mL Standard Deviation 2098.3

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

AUClast of crizotinib is estimated from the crizotinib concentration. It is obtained from Linear/Log trapezoidal method.

Outcome measures

Measure	Crizotinib 150 mg n=6 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Crizotinib	1339 ng*hr/mL Standard Deviation 472.66	3732 ng*hr/mL Standard Deviation 1312.4	6386 ng*hr/mL Standard Deviation 2084.7

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

Outcome measures

Measure	Crizotinib 150 mg n=6 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Maximum Plasma Concentration (Cmax) of Crizotinib	70.54 ng/mL Standard Deviation 25.570	155.6 ng/mL Standard Deviation 50.694	235.8 ng/mL Standard Deviation 60.988

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

Outcome measures

Measure	Crizotinib 150 mg n=6 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Time to Cmax (Tmax) of Crizotinib	5.00 ng/mL Interval 5.0 to 6.0	5.00 ng/mL Interval 4.0 to 6.0	5.00 ng/mL Interval 5.0 to 6.0

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

t1/2 of crizotinib is the time measured for the plasma concentration to decrease by one half. It is obtained from a Loge(2)/kel.

Kel = terminal phase elimination rate constant

Outcome measures

Measure	Crizotinib 150 mg n=6 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Terminal Elimination Half-life (t1/2) of Crizotinib	41.08 hours Standard Deviation 6.7683	29.90 hours Standard Deviation 3.9945	29.13 hours Standard Deviation 3.5753

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

CL/F of crizotinib is obtained from a Dose per AUCinf.

Outcome measures

Measure	Crizotinib 150 mg n=6 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Apparent Oral Clearance (CL/F) of Crizotinib	105.4 liter per hour Standard Deviation 33.926	65.70 liter per hour Standard Deviation 30.500	60.87 liter per hour Standard Deviation 16.936

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

Vz/F of crizotinib is obtained from a Dose / (AUCinf *kel).

Kel = terminal phase elimination rate constant

Outcome measures

Measure	Crizotinib 150 mg n=6 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Apparent Volume of Distribution (Vz/F) of Crizotinib	6170 Liter Standard Deviation 2843.7	2811 Liter Standard Deviation 1765.0	2545 Liter Standard Deviation 958.43

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

Dose normalized (to 150 mg dose) AUC(0-inf) is obtained from AUC(0-inf) / (Dose/150).

Outcome measures

Measure	Crizotinib 150 mg n=6 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Dose Normalized AUC(0-inf) of Crizotinib	1423 ng*hr/mL Standard Deviation 471.52	2284 ng*hr/mL Standard Deviation 787.92	2463 ng*hr/mL Standard Deviation 786.84

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

Dose normalized (to 150 mg dose) AUClast is obtained from AUClast / (Dose/150).

Outcome measures

Measure	Crizotinib 150 mg n=6 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Dose Normalized AUClast of Crizotinib	1339 ng*hr/mL Standard Deviation 472.66	2239 ng*hr/mL Standard Deviation 787.45	2395 ng*hr/mL Standard Deviation 781.75

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

Dose normalized (to 150 mg dose) Cmax is obtained from Cmax / (Dose/150).

Outcome measures

Measure	Crizotinib 150 mg n=6 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Dose Normalized Cmax of Crizotinib	70.54 ng/mL Standard Deviation 25.570	93.36 ng/mL Standard Deviation 30.416	88.41 ng/mL Standard Deviation 22.870

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

AUC(0-inf) of PF-06260182 is estimated from the PF-06260182 concentration. It is obtained from AUClast plus (Clast/kel).

AUClast = area under the plasma concentration-time curve from zero time until the last measurable concentration.

Clast = the last quantifiable concentration. Kel = terminal phase elimination rate constant.

Outcome measures

Measure	Crizotinib 150 mg n=4 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time (AUC0-inf) of Plasma Active Metabolite (PF-06260182)	180.8 ng*hr/mL Standard Deviation 99.369	535.8 ng*hr/mL Standard Deviation 274.23	1046 ng*hr/mL Standard Deviation 549.90

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

AUClast of crizotinib is estimated from the crizotinib concentration. It is obtained from Linear/Log trapezoidal method.

Outcome measures

Measure	Crizotinib 150 mg n=6 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of Plasma Active Metabolite (PF-06260182)	188.1 ng*hr/mL Standard Deviation 81.706	527.2 ng*hr/mL Standard Deviation 273.68	1034 ng*hr/mL Standard Deviation 547.34

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

Outcome measures

Measure	Crizotinib 150 mg n=6 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Maximum Plasma Concentration (Cmax) of Plasma Active Metabolite (PF-06260182)	17.24 ng/mL Standard Deviation 6.2371	37.63 ng/mL Standard Deviation 18.372	54.94 ng/mL Standard Deviation 14.633

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

Outcome measures

Measure	Crizotinib 150 mg n=6 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Time to Cmax (Tmax) of Plasma Active Metabolite (PF-06260182)	5.00 ng/mL Interval 4.0 to 6.0	5.00 ng/mL Interval 4.0 to 6.0	6.00 ng/mL Interval 5.0 to 8.0

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

The metabolic ratio (MR) is calculated by first converting the AUC(0-inf) for both crizotinib and metabolite (PF-06260182) from mass units to molar units.

Outcome measures

Measure	Crizotinib 150 mg n=4 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Metabolite to Parent Ratio AUC(0-inf)	0.1261 ratio Standard Deviation 0.0200	0.1365 ratio Standard Deviation 0.0272	0.1544 ratio Standard Deviation 0.0343

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

The metabolic ratio (MR) is calculated by first converting the AUClast for both crizotinib and metabolite (PF-06260182) from mass units to molar units.

Outcome measures

Measure	Crizotinib 150 mg n=6 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Metabolite to Parent Ratio AUClast	0.1362 ratio Standard Deviation 0.0262	0.1370 ratio Standard Deviation 0.0272	0.1571 ratio Standard Deviation 0.0347

PRIMARY outcome

Timeframe: 0, 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, 144 hours post-dose

The metabolic ratio (MR) is calculated by first converting the Cmax for both crizotinib and metabolite (PF-06260182) from mass units to molar units.

Outcome measures

Measure	Crizotinib 150 mg n=6 Participants A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 Participants A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 Participants A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Metabolite to Parent Ratio Cmax	0.2371 ratio Standard Deviation 0.0833	0.2346 ratio Standard Deviation 0.0441	0.2260 ratio Standard Deviation 0.0429

Adverse Events

Crizotinib 150 mg

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Crizotinib 250 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Crizotinib 400 mg

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Crizotinib 150 mg n=6 participants at risk A 150 mg single dose of crizotinib administered as one 50 mg Immediate Release Tablet (IRT) and one 100 mg IRT	Crizotinib 250 mg n=6 participants at risk A 250 mg single dose of crizotinib administered as one 50 mg IRT and two 100 mg IRTs	Crizotinib 400 mg n=6 participants at risk A 400 mg single dose of crizotinib administered as four 100 mg IRTs.
Gastrointestinal disorders Nausea	16.7% 1/6 • For serious adverse event, up to 28 days after the last administration of the study drugs 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.	0.00% 0/6 • For serious adverse event, up to 28 days after the last administration of the study drugs 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.	0.00% 0/6 • For serious adverse event, up to 28 days after the last administration of the study drugs 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.
Investigations Alanine aminotransferase increased	16.7% 1/6 • For serious adverse event, up to 28 days after the last administration of the study drugs 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.	0.00% 0/6 • For serious adverse event, up to 28 days after the last administration of the study drugs 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.	0.00% 0/6 • For serious adverse event, up to 28 days after the last administration of the study drugs 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.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/6 • For serious adverse event, up to 28 days after the last administration of the study drugs 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.	0.00% 0/6 • For serious adverse event, up to 28 days after the last administration of the study drugs 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.	16.7% 1/6 • For serious adverse event, up to 28 days after the last administration of the study drugs 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.

Additional Information

Pfizer ClinicalTrials.gov Call Center

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Phone: 1-800-718-1021

Email: ClinicalTrials.gov_Inquiries@pfizer.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER