Hepatic Impairment Study For Crizotinib In Advanced Cancer Patients

Sponsor

Pfizer (Industry)

Overall Status

Completed

CT.gov ID

NCT01576406

Collaborator

(none)

Enrollment

Locations

Arms

Actual Duration (Months)

4.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to evaluate the potential effect of hepatic impairment on the pharmacokinetics and safety of crizotinib in advanced cancer patients. Advanced cancer patients with mild, moderate or severe liver dysfunction as well as patients with normal liver function will be enrolled in this study.

Condition or Disease	Intervention/Treatment	Phase
Advanced Cancer	Drug: crizotinib Drug: crizotinib Drug: crizotinib Drug: crizotinib Drug: crizotinib	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

88 participants

Allocation:

Non-Randomized

Masking:

None (Open Label)

Primary Purpose:

Basic Science

Official Title:

A Phase I Study To Evaluate The Effect Of Hepatic Impairment On The Pharmacokinetics And Safety Of Crizotinib In Advanced Cancer Patients

Actual Study Start Date :

Jul 1, 2012

Actual Primary Completion Date :

Jun 1, 2016

Actual Study Completion Date :

Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A1: normal hepatic function	Drug: crizotinib crizotinib 250 mg twice a day
Experimental: A2: normal hepatic function	Drug: crizotinib crizotinib 250 mg once a day
Experimental: B: mild hepatic impairment	Drug: crizotinib crizotinib 250 mg twice a day
Experimental: C: moderate hepatic impairment	Drug: crizotinib crizotinib 250 mg once a day
Experimental: D: severe hepatic impairment	Drug: crizotinib crizotinib 250 mg once a day

Outcome Measures

Primary Outcome Measures

Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Area under the plasma concentration-time curve from time zero to the quantifiable concentration at the end of dosing interval (tau hours post-dose, where tau was 12 hours for twice daily dosing and 24 hours for once daily dosing) of Cycle 2 Day 1.
Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]

Secondary Outcome Measures

Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of Crizotinib: Cycle 1 Day 1 [Cycle 1 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 1 Day 1 [Cycle 1 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib: Cycle 1 Day 1 [Cycle 1 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Minimum Observed Plasma Concentration (Cmin) of Crizotinib: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of Crizotinib: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Plasma Accumulation Ratio (Rac) of Crizotinib [Cycle 1 Day 1 and Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Rac was defined as the ratio of AUCtau of Cycle 2 Day 1 to AUCtau of Cycle 1 Day 1, where AUCtau was area under the plasma concentration-time curve from time zero to the quantifiable concentration at the end of dosing interval (tau hours post-dose, where tau was 12 hours for twice daily dosing and 24 hours for once daily dosing).
Apparent Oral Clearance (CL/F) of Crizotinib: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent oral clearance was obtained by dividing study drug dose with AUCtau, where AUCtau was area under the plasma concentration-time curve from time zero to the quantifiable concentration at the end of dosing interval (tau hours post-dose, where tau was 12 hours for twice daily dosing and 24 hours for once daily dosing) of Cycle 2 Day 1.
Fraction of Unbound Crizotinib in Plasma: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Fraction of unbound Crizotinib concentration in plasma was defined as the ratio of unbound Crizotinib concentration to the total Crizotinib concentration.
Unbound Area Under the Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of Crizotinib: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Unbound area under the plasma concentration-time curve from time zero to the last quantifiable plasma concentration post-dose of Cycle 2 day 1.
Unbound Area Under Plasma Concentration-Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Unbound area under the plasma concentration-time curve from time zero to the quantifiable concentration at the end of dosing interval (tau hours post-dose, where tau was 12 hours for twice daily dosing and 24 hours for once daily dosing) of Cycle 2 Day 1.
Unbound Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Area under the plasma concentration-time curve from time zero to the quantifiable concentration at the end of dosing interval (tau hours postdose, where tau was 12 hours for twice daily dosing and 24 hours for once daily dosing) of Cycle 2 Day 1. AUCtau of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast) of PF-06260182: Cycle 1 Day 1 [Cycle 1 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
AUClast of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1 [Cycle 1 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Cmax of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Cmax of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 1 Day 1 [Cycle 1 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Tmax of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Tmax of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Metabolite Ratio for Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Metabolite ratio for AUCtau was defined as the ratio of AUCtau of metabolite (PF-06260182) to AUCtau of parent drug (Crizotinib), where AUCtau was the area under the plasma concentration-time curve from time zero to the quantifiable concentration at the end of dosing interval (tau was 12 hours for twice daily dosing and 24 hours for once daily dosing) of Cycle 2 Day 1.
Metabolite Ratio for Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of PF-06260182: Cycle 1 Day 1 [Cycle 1 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Metabolite ratio for AUClast was defined as the ratio of AUClast of metabolite (PF-06260182) to AUClast of parent drug (Crizotinib), where AUClast was area under the plasma concentration-time curve from time zero to the last quantifiable plasma concentration post-dose of Cycle 1 Day 1.
Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1 [Cycle 1 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Metabolite ratio for Cmax was defined as the ratio of Cmax of metabolite (PF-06260182) to Cmax of parent drug (Crizotinib), where Cmax was maximum observed plasma concentration post-dose of Cycle 1 Day 1.
Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Metabolite ratio for Cmax was defined as the ratio of Cmax of metabolite (PF-06260182) to Cmax of parent drug (Crizotinib), where Cmax was maximum observed plasma concentration post-dose of Cycle 2 Day 1.
Fraction of Unbound PF-06260182 in Plasma: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Fraction of unbound PF-06260182 (a metabolite of Crizotinib) in plasma was defined as the ratio of unbound PF-06260182 concentration in plasma to the total PF-06260182 concentration.
Unbound Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast) of PF-06260182: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Unbound AUClast of PF-06260182 (a metabolite of Crizotinib) is reported in this outcome measure.
Unbound Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Unbound area under the plasma concentration-time curve from time zero to the quantifiable concentration at the end of dosing interval (tau hours post-dose, where tau was 12 hours for twice daily dosing and 24 hours for once daily dosing) of Cycle 2 Day 1. Unbound AUCtau of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Unbound Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Unbound Cmax of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.

Other Outcome Measures

Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
AUCdaily of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1 [Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose]
Unbound AUCdaily of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure, where AUCdaily was area under the plasma concentration time curve as daily exposure post-dose.
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [From initiation of treatment up to follow-up period (up to 4 years)]
An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 4 years that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.
Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade [From initiation of treatment up to follow-up period (up to 4 years)]
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events [CTCAE] Version 4.0. Grade 1 =mild; Grade 2 =moderate; Grade 3 =severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4 =life-threatening or disabling, urgent intervention indicated; Grade 5 =death. Treatment-emergent events were events between first dose of study drug and up to 4 years that were absent before treatment that worsened relative to pretreatment state. If the same participant in a given treatment had more than 1 adverse event, only the maximum CTCAE was reported.
Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) [From initiation of treatment up to follow-up period (up to 4 years)]
Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both serious and non-serious adverse events.
Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities [Baseline up to end of treatment (up to 728 days)]
Anemia(grade[g]1:Less than[<] Lower limit of normal[LLN] to 10gram per[/] deciliter[g/dL],g2:<10 to 8g/dL,g3:<8g/dL,g4:lifethreatening);platelet (g1:<LLN to 75*10^3/millimeter[mm]^3,g2:<75*10^3/mm^3 to 50*10^3/mm^3,g3:<50*10^3/mm^3 to 25*10^3/mm^3,g4:<25*10^3/mm^3);lymphopenia(g1:<LLN to 8*10^2/mm^3,g2:<8*10^2 to 5*10^2/mm^3,g3:<5*10^2 to 2*10^2/mm^3,g4:<2*10^2/mm^3);neutrophil (Absolute)(g1:<LLN to 15*10^2/mm^3,g2:<15*10^2 to 10*10^2/mm^3,g3:<10*10^2 to 5*10^2/mm^3,g4:<5*10^2/mm^3);white blood cell count(g1:<LLN to 3*10^3/mm^3,g2:<3*10^3 to 2*10^3/mm^3,g3:<2*10^3 to 1*10^3/mm^3,g4:<1*10^3/mm^3);hemoglobin(g1:increase in hemoglobin level>0 to 2 g/dL above ULN or above baseline if baseline is above ULN,g2:increase in hemoglobin level>2 to 4g/dL above ULN or above baseline if baseline is above ULN,g3:increase in hemoglobin level>4 g/dL above ULN or above baseline if baseline is above ULN). Only categories with atleast 1 participant with abnormality are reported in this outcome measure.
Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities [Baseline up to end of treatment (up to 728 days)]
ALT/AST(grade[g]1:>ULN-3*ULN,g2:>3-5*ULN,g3:>5-20*ULN,g4:>20*ULN);AP(g1:>ULN-2.5*ULN,g2:>2.5-5*ULN,g3:>5-20*ULN,g4:>20*ULN);CR(g1:>ULN-1.5*ULN,g2:>1.5-3*ULN,g3:>3-6*ULN,g4:>6*ULN);hyperglycemia(g1:>ULN-160mg/dL,g2:>160-250mg/dL,g3:>250-500mg/dL,g4:>500mg/dL);bilirubin(total)(g1:>ULN-1.5*ULN,g2:>1.5-3*ULN,g3:>3-10*ULN,g4:>10*ULN);hypoglycemia(g1:<LLN-55mg/dL,g2:<55-40mg/dL,g3:<40-30mg/dL,g4:<30mg/dL);hyperkalemia(g1:>ULN-5.5mmol/L,g2:>5.5-6mmol/L,g3:>6-7mmol/L,g4:>7mmol/L);hypokalemia(g1:<LLN-3mmol/L,g2:<LLN-3mmol/L,g3:<3-2.5mmol/L,g4:<2.5mmol/L);hypermagnesemia(g1:>ULN-3mg/dL,g3:>3-8mg/dL,g4:>8mg/dL);hypocalcemia(g1:<LLN-8mg/dL,g2:<8-7mg/dL,g3:<7-6mg/dL,g4:<6mg/dL);hypomagnesemia(g1:<LLN-1.2mg/dL,g2:<1.2-0.9mg/dL,g3:<0.9-0.7mg/dL,g4:<0.7mg/dL);hyponatremia(g1:<LLN-130mmol/L,g3:<130-120mmol/L,g4:<120mmol/L);hypoalbuminemia(g1:<LLN-3g/dL,g2:<3-2g/dL,g3:<2g/dL,g4:lifethreatening);hypophosphatemia(g1:<LLN-2.5mg/dL,g2:<2.5-2mg/dL,g3:<2-1mg/dL,g4:<1mg/dL).Participant>=1abnormality given.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings [Baseline up to end of treatment (up to 728 days)]
Criteria for abnormal value of ECG parameters: maximum increase from baseline (IFB) in QT interval using Fridericia's correction (QTcF)/QT interval using Bazett's correction (QTcB) range from less than (<)30 millisecond (msec), 30 to <60, greater than or equal to (>=)60 msec; maximum post-dose QTcF/QTcB ranges from <450 msec, 450 to <480 msec, 480 to <500, and >=500 msec; PR interval: >=50 percent (%) increase when baseline <200 msec; or increase >=25% when baseline less than or equal to (<=)200 msec; QRS interval: >=50% increase when baseline <100 msec; >=25% increase when baseline >=100 msec. Only categories which included atleast 1 participant with abnormality are reported in this outcome measure.
Number of Participants With Abnormal Fundoscopy Examination Findings [Baseline up to end of treatment (up to 728 days)]
Fundoscopy examination included an examination of the vitreous body, retina macula, retina non-macula, optic nerve head, optic disc notching and fundus using the category of the examination status (normal, mild, moderate, or severe). In this outcome measure, number of participants with abnormal fundoscopy values identified by investigator were reported.
Objective Response Rate (ORR) [Baseline, every 8 weeks until disease progression or unacceptable toxicity up to end of treatment (up to 728 days)]
ORR was defined as percentage of participants with confirmed complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors (RECIST) version 1.1. In case of target lesions CR was defined as the disappearance of all target lesions and in case nodal disease included in the sum of target lesions. The nodes decreased to normal size (<10 mm). In case of non-target lesions disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Confirmed responses were those who persisted on repeat imaging study at least 4 weeks after the initial documentation of response.
Duration of Response (DR) [Baseline, every 8 weeks until disease progression or unacceptable toxicity up to end of treatment (up to 728 days)]
DR was defined as the time from date of first documentation of CR or PR to first documentation of objective tumor progression or death due to any cause, whichever occurred first. In case of target lesions CR was defined as the disappearance of all target lesions and in case nodal disease included in the sum of target lesions. The nodes decreased to normal size (<10 mm). In case of non-target lesions disappearance of all non-target lesions and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Objective tumor progression as per RECIST version 1.1 was defined as >=20% increase in sum of diameters of target lesions taking as a reference smallest sum of diameters recorded since treatment started, or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. DR was estimated using Kaplan-Meier method.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically or cytologically confirmed solid malignancy or lymphoma that is metastatic or unresectable, and for which standard curative or palliative measures do not exist, or are no longer effective. In case of hepatocellular carcinoma, the diagnosis should be based on at least one of the following:

The presence of at least one lesion, measuring ≥ 2 cm, with characteristic arterial enhancement and venous washout in the setting of liver cirrhosis and/or hepatitis B or C infection.
The presence of liver lesion(s) (as defined in a.) with AFP ≥ 400 ng/mL.
Tissue confirmation.

Biliary obstruction for whom a biliary drain or stent has been placed are eligible, provided that the drain or stent have been in place for at least 10 days prior to the first dose of crizotinib, and the liver function has stabilized as defined by 2 measurements at least 5 days apart that put the patient in the same hepatic dysfunction stratum as defined in Section 3.
Presence of gliomas and brain metastases only if neurologically stable and treated without ongoing requirement for corticosteroids for at least 2 weeks.
Any prior systemic therapy (e.g., chemotherapy, molecularly targeted agent, immunotherapy, etc.) or major surgery must have been completed at least 30 days (or as determined by the local requirement, whichever is longer), or at least 5 half lives for drugs with half lives of 6 days or longer prior to initiation of crizotinib treatment. Any prior radiation (except palliative) or minor surgeries/procedures must have been completed at least 2 weeks prior to the initiation of crizotinib treatment. Palliative radiation (≤ 10 fractions) must have been completed 48 hours prior to the initiation of crizotinib treatment. Any acute toxicity must have recovered to Grade ≤1 (except alopecia).
Eastern Cooperative Oncology Group [ECOG] performance status 0-2.
Adequate organ function for patients receiving crizotinib therapy as defined by the following criteria:

Bone marrow function

Absolute neutrophil count (ANC) ≥ 750/uL
Platelets ≥ 30,000/uL
Hemoglobin ≥ 8.0 g/dL (≥ 7.0 g/dL for hematologic malignancy) Renal function
Creatinine ≤ 1.5 x ULN or CrCl > 60 mL/min/1.73 m2 for patients with serum creatinine levels above institutional 1.5 x ULN
Male and female patients of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 28 days after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.

Exclusion Criteria:

Untreated esophageal varices observed on EGD or imaging study; however, patients with known portal hypertension and evidence of varices on EGD or imaging study who have undergone appropriate therapy as indicated within the last 6 months (if applicable) are eligible for enrollment.
Uncontrolled ascites that is not stable with medical management (i.e., on diuretics and salt restriction) as defined by requiring therapeutic paracentesis more than once every 4 weeks.
Episodes of hepatic encephalopathy within the last 4 weeks. Patients with prior episodes of hepatic encephalopathy who are clinically stable on lactulose, neomycin, and/or xifaxan therapy are allowed.
Prior therapy with crizotinib.
Spinal cord compression.
Carcinomatous meningitis or leptomeningeal disease
Any of the following within the 6 months prior to starting study treatment: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, or cerebrovascular accident including transient ischemic attack.
Symptomatic congestive heart failure.
Ongoing cardiac dysrhythmias of NCI CTCAE Grade ≥ 2, uncontrolled atrial fibrillation of any grade, or an average of triplicate QTc interval >470 msec.
History of extensive disseminated/bilateral or known presence of interstitial fibrosis or interstitial lung disease, including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, and pulmonary fibrosis, but not history of prior radiation pneumonitis.
Active hemolysis or evidence of biliary sepsis.
Pregnant females; breastfeeding females; males and females of childbearing potential; males and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least 28 days after last dose of investigational product; males and females of childbearing potential not using two (2) methods of highly effective contraception or not agreeing to continue two (2) methods of highly effective contraception for at least 28 days after last dose of investigational product.
Use of drugs or foods that are known strong CYP3A4 inhibitors, including but not limited to atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, troleandomycin, voriconazole, and grapefruit or grapefruit juice.
Use of drugs that are known strong CYP3A4 inducers, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort.
Use of drugs that are CYP3A4 substrates with narrow therapeutic indices, including but not limited to dihydroergotamine, ergotamine, and pimozide.
Other severe acute or chronic medical (may include severe gastrointestinal conditions such as chronic diarrhea or ulcer disease) or psychiatric conditions, or laboratory abnormalities that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of the study results and, in the judgment of the investigator, would make the patient inappropriate for study entry.
Patients who had prior major gastrointestinal surgery removing part of gastrointestinal tract and/or gall bladder.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Keck Hospital of USC	Los Angeles	California	United States	90033
2	LAC&USC Medical Center	Los Angeles	California	United States	90033
3	USC/Norris Comprehensive Cancer Center / Investigational Drug Services	Los Angeles	California	United States	90033
4	USC/Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
5	Anschutz Cancer Pavilion, Room 2224, c/o Melinda Friesleben, Pharm D	Aurora	Colorado	United States	80045
6	University of Colorado Denver - Clinical Translational Research Center	Aurora	Colorado	United States	80045
7	University of Colorado Denver, Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
8	University of Colorado Denver, Anschutz Inpatient Pavillion	Aurora	Colorado	United States	80045
9	Emory University Hospital Midtown Laboratory	Atlanta	Georgia	United States	30308
10	Emory University Hospital	Atlanta	Georgia	United States	30322
11	Investigational Drug Service: The Emory Clinic Bldg A	Atlanta	Georgia	United States	30322
12	The Emory Clinic	Atlanta	Georgia	United States	30322
13	Winship Cancer Institute	Atlanta	Georgia	United States	30322
14	University Hospital East	Columbus	Ohio	United States	43205
15	Investigational Drug Services	Columbus	Ohio	United States	43210
16	James Cancer Hospital	Columbus	Ohio	United States	43210
17	The Ohio State University, Wexner Medical Center	Columbus	Ohio	United States	43210
18	Martha Morehouse Medical Plaza	Columbus	Ohio	United States	43221
19	Cancer Therapy & Research Center at UTHSCSA	San Antonio	Texas	United States	78229
20	Medical Arts and Research Center-MARC	San Antonio	Texas	United States	78229

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:

NCT01576406

Other Study ID Numbers:

A8081012

First Posted:

Apr 12, 2012

Last Update Posted:

Oct 25, 2018

Last Verified:

Jan 1, 2018

Keywords provided by Pfizer

Additional relevant MeSH terms:

Neoplasms

Crizotinib

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Period Title: Overall Study
STARTED	11	15	20	10	16	16
COMPLETED	5	7	4	1	8	4
NOT COMPLETED	6	8	16	9	8	12

Baseline Characteristics

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily	Total
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.	Total of all reporting groups
Overall Participants	11	15	20	10	16	16	88
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.7 (15.64)	62.9 (10.35)	61.2 (10.14)	59.2 (8.85)	60.3 (7.87)	59.0 (6.04)	60.3 (9.77)
Sex: Female, Male (Count of Participants)
Female	4 36.4%	6 40%	7 35%	2 20%	6 37.5%	6 37.5%	31 35.2%
Male	7 63.6%	9 60%	13 65%	8 80%	10 62.5%	10 62.5%	57 64.8%

Outcome Measures

1. Primary Outcome

Title	Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1
Description	Area under the plasma concentration-time curve from time zero to the quantifiable concentration at the end of dosing interval (tau hours post-dose, where tau was 12 hours for twice daily dosing and 24 hours for once daily dosing) of Cycle 2 Day 1.
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set:Cycle 2 Day 1(C2D1)full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [nanogramhour per milliliter (nghr/mL)]	3552 (48)	2712 (66)	3238 (73)	2305 (83)	4057 (58)	4596 (63)

2. Primary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 2 Day 1
Description
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]	375.1 (50)	283.9 (65)	342.1 (68)	152.9 (58)	408.3 (56)	272.4 (29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Hepatic Function: Crizotinib 250 mg Twice Daily, Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily
	Comments	Confidence interval (CI): Geometric mean ratio and 90 percent (%) CI were derived from analysis of variance (ANOVA) model.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	91.20
	Confidence Interval	(2-Sided) 90% 57.47 to 144.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily, Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily
	Comments	CI: Geometric mean ratio and 90% CI were derived from ANOVA model.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	143.82
	Confidence Interval	(2-Sided) 90% 89.11 to 232.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Normal Hepatic Function: Crizotinib 250 mg Twice Daily, Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily
	Comments	CI: Geometric mean ratio and 90% CI were derived from ANOVA model.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	108.87
	Confidence Interval	(2-Sided) 90% 70.13 to 168.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Normal Hepatic Function: Crizotinib 250 mg Twice Daily, Severe Hepatic Impairment Crizotinib 250 mg Once Daily
	Comments	CI: Geometric mean ratio and 90% CI were derived from ANOVA model.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Geometric mean ratio
	Estimated Value	72.63
	Confidence Interval	(2-Sided) 90% 49.07 to 107.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of Crizotinib: Cycle 1 Day 1
Description
Time Frame	Cycle 1 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	9	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	732.3 (84)	520.8 (49)	557.5 (78)	610.4 (128)	684.9 (89)	856.7 (57)

4. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 1 Day 1
Description
Time Frame	Cycle 1 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set. Here, 'N' signifies those participants who were evaluable for this measure.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	9	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	101.9 (92)	84.52 (67)	102.3 (66)	57.74 (112)	99.59 (88)	90.69 (63)

5. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib: Cycle 1 Day 1
Description
Time Frame	Cycle 1 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set. Here, 'N' signifies those participants who were evaluable for this measure.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	9	7	8	6
Median (Full Range) [hour]	4.00	4.00	4.00	2.02	4.00	3.00

6. Secondary Outcome

Title	Minimum Observed Plasma Concentration (Cmin) of Crizotinib: Cycle 2 Day 1
Description
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	238.6 (52)	170.9 (75)	179.1 (101)	47.44 (376)	287.0 (58)	135.5 (102)

7. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of Crizotinib: Cycle 2 Day 1
Description
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
Data for this outcome measure was not estimated, since few secondary PK parameters listed in the protocol and/or SAP were not estimated, due to change in planned analysis. However, it did not affect the interpretation of the final PK data.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	0	0	0	0	0	0

8. Secondary Outcome

Title	Plasma Accumulation Ratio (Rac) of Crizotinib
Description	Rac was defined as the ratio of AUCtau of Cycle 2 Day 1 to AUCtau of Cycle 1 Day 1, where AUCtau was area under the plasma concentration-time curve from time zero to the quantifiable concentration at the end of dosing interval (tau hours post-dose, where tau was 12 hours for twice daily dosing and 24 hours for once daily dosing).
Time Frame	Cycle 1 Day 1 and Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
Data for this outcome measure was not estimated, since few secondary PK parameters listed in the protocol and/or SAP were not estimated, due to change in planned analysis. However, it did not affect the interpretation of the final PK data.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	0	0	0	0	0	0

9. Secondary Outcome

Title	Apparent Oral Clearance (CL/F) of Crizotinib: Cycle 2 Day 1
Description	Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent oral clearance was obtained by dividing study drug dose with AUCtau, where AUCtau was area under the plasma concentration-time curve from time zero to the quantifiable concentration at the end of dosing interval (tau hours post-dose, where tau was 12 hours for twice daily dosing and 24 hours for once daily dosing) of Cycle 2 Day 1.
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [Liter/hour]	70.39 (48)	73.79 (66)	77.21 (73)	108.5 (83)	49.26 (58)	54.36 (63)

10. Secondary Outcome

Title	Fraction of Unbound Crizotinib in Plasma: Cycle 2 Day 1
Description	Fraction of unbound Crizotinib concentration in plasma was defined as the ratio of unbound Crizotinib concentration to the total Crizotinib concentration.
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ratio]	0.03624 (26)	0.03066 (27)	0.04315 (31)	0.05406 (20)	0.04152 (34)	0.03523 (46)

11. Secondary Outcome

Title	Unbound Area Under the Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of Crizotinib: Cycle 2 Day 1
Description	Unbound area under the plasma concentration-time curve from time zero to the last quantifiable plasma concentration post-dose of Cycle 2 day 1.
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
Data for this outcome measure was not estimated, since few secondary PK parameters listed in the protocol and/or SAP were not estimated, due to change in planned analysis. However, it did not affect the interpretation of the final PK data.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	0	0	0	0	0	0

12. Secondary Outcome

Title	Unbound Area Under Plasma Concentration-Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1
Description	Unbound area under the plasma concentration-time curve from time zero to the quantifiable concentration at the end of dosing interval (tau hours post-dose, where tau was 12 hours for twice daily dosing and 24 hours for once daily dosing) of Cycle 2 Day 1.
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	128.7 (38)	83.08 (73)	139.7 (94)	124.6 (85)	168.6 (59)	161.9 (48)

13. Secondary Outcome

Title	Unbound Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 2 Day 1
Description
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	13.59 (41)	8.703 (74)	14.77 (93)	8.271 (62)	16.96 (56)	9.608 (34)

14. Secondary Outcome

Title	Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1
Description	Area under the plasma concentration-time curve from time zero to the quantifiable concentration at the end of dosing interval (tau hours postdose, where tau was 12 hours for twice daily dosing and 24 hours for once daily dosing) of Cycle 2 Day 1. AUCtau of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	1087 (43)	717.4 (81)	480.3 (168)	200.0 (48)	391.8 (118)	434.0 (96)

15. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast) of PF-06260182: Cycle 1 Day 1
Description	AUClast of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Time Frame	Cycle 1 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set. Here, 'N' signifies those participants who were evaluable for this measure.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	9	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	272.4 (80)	166.5 (31)	90.71 (153)	64.90 (103)	53.36 (139)	59.61 (81)

16. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1
Description	Cmax of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Time Frame	Cycle 1 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set. Here, 'N' signifies those participants who were evaluable for this measure.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	9	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	35.48 (86)	24.12 (33)	13.54 (153)	4.869 (95)	6.995 (152)	4.088 (88)

17. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1
Description	Cmax of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	108.5 (43)	73.47 (76)	50.34 (164)	12.43 (55)	39.32 (120)	25.15 (110)

18. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 1 Day 1
Description	Tmax of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Time Frame	Cycle 1 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set. Here, 'N' signifies those participants who were evaluable for this measure.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	9	7	8	6
Median (Full Range) [hour]	6.04	4.00	4.00	6.08	8.00	7.00

19. Secondary Outcome

Title	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 2 Day 1
Description	Tmax of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Median (Full Range) [hour]	6.00	4.03	4.00	6.00	0	6.69

20. Secondary Outcome

Title	Metabolite Ratio for Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1
Description	Metabolite ratio for AUCtau was defined as the ratio of AUCtau of metabolite (PF-06260182) to AUCtau of parent drug (Crizotinib), where AUCtau was the area under the plasma concentration-time curve from time zero to the quantifiable concentration at the end of dosing interval (tau was 12 hours for twice daily dosing and 24 hours for once daily dosing) of Cycle 2 Day 1.
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ratio]	0.2968 (17)	0.2569 (31)	0.1439 (74)	0.08402 (65)	0.09360 (47)	0.09162 (47)

21. Secondary Outcome

Title	Metabolite Ratio for Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of PF-06260182: Cycle 1 Day 1
Description	Metabolite ratio for AUClast was defined as the ratio of AUClast of metabolite (PF-06260182) to AUClast of parent drug (Crizotinib), where AUClast was area under the plasma concentration-time curve from time zero to the last quantifiable plasma concentration post-dose of Cycle 1 Day 1.
Time Frame	Cycle 1 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set. Here, 'N' signifies those participants who were evaluable for this measure.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	9	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ratio]	0.3608 (18)	0.3104 (30)	0.1577 (60)	0.1032 (72)	0.07566 (42)	0.06753 (21)

22. Secondary Outcome

Title	Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1
Description	Metabolite ratio for Cmax was defined as the ratio of Cmax of metabolite (PF-06260182) to Cmax of parent drug (Crizotinib), where Cmax was maximum observed plasma concentration post-dose of Cycle 1 Day 1.
Time Frame	Cycle 1 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set. Here, 'N' signifies those participants who were evaluable for this measure.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	9	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ratio]	0.3378 (25)	0.2769 (41)	0.1284 (70)	0.08178 (66)	0.06809 (47)	0.04373 (42)

23. Secondary Outcome

Title	Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1
Description	Metabolite ratio for Cmax was defined as the ratio of Cmax of metabolite (PF-06260182) to Cmax of parent drug (Crizotinib), where Cmax was maximum observed plasma concentration post-dose of Cycle 2 Day 1.
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ratio]	0.2804 (19)	0.2511 (31)	0.1428 (73)	0.07881 (58)	0.09337 (49)	0.08954 (90)

24. Secondary Outcome

Title	Fraction of Unbound PF-06260182 in Plasma: Cycle 2 Day 1
Description	Fraction of unbound PF-06260182 (a metabolite of Crizotinib) in plasma was defined as the ratio of unbound PF-06260182 concentration in plasma to the total PF-06260182 concentration.
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ratio]	0.03797 (11)	0.03822 (16)	0.04857 (16)	0.05788 (22)	0.05031 (10)	0.05177 (13)

25. Secondary Outcome

Title	Unbound Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast) of PF-06260182: Cycle 2 Day 1
Description	Unbound AUClast of PF-06260182 (a metabolite of Crizotinib) is reported in this outcome measure.
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
Data for this outcome measure was not estimated, since few secondary PK parameters listed in the protocol and/or SAP were not estimated, due to change in planned analysis. However, it did not affect the interpretation of the final PK data.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	0	0	0	0	0	0

26. Secondary Outcome

Title	Unbound Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1
Description	Unbound area under the plasma concentration-time curve from time zero to the quantifiable concentration at the end of dosing interval (tau hours post-dose, where tau was 12 hours for twice daily dosing and 24 hours for once daily dosing) of Cycle 2 Day 1. Unbound AUCtau of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	41.26 (36)	27.40 (99)	23.35 (181)	11.56 (49)	19.71 (119)	22.49 (79)

27. Secondary Outcome

Title	Unbound Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1
Description	Unbound Cmax of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	4.119 (36)	2.806 (94)	2.445 (178)	0.7194 (50)	1.977 (122)	1.301 (93)

28. Other Pre-specified Outcome

Title	Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: Cycle 2 Day 1
Description
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	7107 (48)	5422 (66)	6476 (73)	2305 (83)	8108 (58)	4596 (63)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Hepatic Function: Crizotinib 250 mg Twice Daily, Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily
	Comments	CI: Geometric mean ratio and 90% CI were derived from ANOVA model.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Percentage of ratio of geometric mean
	Estimated Value	91.12
	Confidence Interval	(2-Sided) 90% 56.56 to 146.79
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily, Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily
	Comments	CI: Geometric mean ratio and 90% CI were derived from ANOVA model.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Percentage of ratio of geometric mean
	Estimated Value	149.54
	Confidence Interval	(2-Sided) 90% 91.85 to 243.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Normal Hepatic Function: Crizotinib 250 mg Twice Daily, Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily
	Comments	CI: Geometric mean ratio and 90% CI were derived from ANOVA model.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Percentage of ratio of geometric mean
	Estimated Value	114.08
	Confidence Interval	(2-Sided) 90% 73.57 to 176.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Normal Hepatic Function: Crizotinib 250 mg Twice Daily, Severe Hepatic Impairment Crizotinib 250 mg Once Daily
	Comments	CI: Geometric mean ratio and 90% CI were derived from ANOVA model.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Percentage of ratio of geometric mean
	Estimated Value	64.67
	Confidence Interval	(2-Sided) 90% 39.50 to 105.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

29. Other Pre-specified Outcome

Title	Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: Cycle 2 Day 1
Description
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	257.7 (38)	166.1 (73)	279.4 (95)	124.6 (85)	337.0 (59)	161.9 (48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Normal Hepatic Function: Crizotinib 250 mg Twice Daily, Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily
	Comments	CI: Geometric mean ratio and 90% CI were derived from ANOVA model.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Percentage of ratio of geometric mean
	Estimated Value	108.43
	Confidence Interval	(2-Sided) 90% 63.47 to 185.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily, Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily
	Comments	CI: Geometric mean ratio and 90% CI were derived from ANOVA model.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Percentage of ratio of geometric mean
	Estimated Value	202.89
	Confidence Interval	(2-Sided) 90% 120.96 to 340.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Normal Hepatic Function: Crizotinib 250 mg Twice Daily, Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily
	Comments	CI: Geometric mean ratio and 90% CI were derived from ANOVA model.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Percentage of ratio of geometric mean
	Estimated Value	130.78
	Confidence Interval	(2-Sided) 90% 86.61 to 197.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Normal Hepatic Function: Crizotinib 250 mg Twice Daily, Severe Hepatic Impairment Crizotinib 250 mg Once Daily
	Comments	CI: Geometric mean ratio and 90% CI were derived from ANOVA model.
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Percentage of ratio of geometric mean
	Estimated Value	62.82
	Confidence Interval	(2-Sided) 90% 42.54 to 92.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

30. Other Pre-specified Outcome

Title	Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1
Description	AUCdaily of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure.
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	2173 (43)	1435 (81)	961.2 (168)	200.0 (48)	784.0 (117)	434.0 (96)

31. Other Pre-specified Outcome

Title	Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1
Description	Unbound AUCdaily of PF-06260182, (a metabolite of Crizotinib) is reported in this outcome measure, where AUCdaily was area under the plasma concentration time curve as daily exposure post-dose.
Time Frame	Cycle 2 Day 1- Twice daily dosing: pre-dose and 1, 2, 4, 6, 8, 12 hours post-dose; Once daily dosing: pre-dose and 1, 2, 4, 6, 8, 24 hours post-dose

Outcome Measure Data

Analysis Population Description
PK evaluable set: C2D1 full PK collected;no dose change;atleast 14 days of constant dosing before C2D1 or>80% of Crizotinib during 14 days prior to C2D1;not vomited Crizotinib on same day of PK collection on C2D1;no prior major GI surgery;11 days of constant dosing instead of 14 days before C2D1 but met all other PK evaluable criteria.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	8	9	10	7	8	6
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	82.56 (36)	54.85 (99)	46.66 (181)	11.56 (49)	39.41 (119)	22.49 (79)

32. Other Pre-specified Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 4 years that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.
Time Frame	From initiation of treatment up to follow-up period (up to 4 years)

Outcome Measure Data

Analysis Population Description
Safety analysis population included all enrolled participants who received at least 1 dose of Crizotinib on Cycle 1, Day 1.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	11	15	20	10	16	16
AEs	11 100%	15 100%	20 100%	9 90%	16 100%	16 100%
SAEs	7 63.6%	8 53.3%	13 65%	6 60%	14 87.5%	14 87.5%

33. Other Pre-specified Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AE was assessed according to severity grading based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events [CTCAE] Version 4.0. Grade 1 =mild; Grade 2 =moderate; Grade 3 =severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4 =life-threatening or disabling, urgent intervention indicated; Grade 5 =death. Treatment-emergent events were events between first dose of study drug and up to 4 years that were absent before treatment that worsened relative to pretreatment state. If the same participant in a given treatment had more than 1 adverse event, only the maximum CTCAE was reported.
Time Frame	From initiation of treatment up to follow-up period (up to 4 years)

Outcome Measure Data

Analysis Population Description
Safety analysis population included all enrolled participants who received at least 1 dose of Crizotinib on Cycle 1, Day 1.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	11	15	20	10	16	16
Grade 1 AEs	1 9.1%	2 13.3%	2 10%	0 0%	0 0%	0 0%
Grade 2 AEs	2 18.2%	6 40%	5 25%	1 10%	0 0%	1 6.3%
Grade 3 AEs	6 54.5%	3 20%	5 25%	2 20%	9 56.3%	8 50%
Grade 4 AEs	0 0%	1 6.7%	2 10%	1 10%	2 12.5%	0 0%
Grade 5 AEs	2 18.2%	3 20%	6 30%	5 50%	5 31.3%	7 43.8%

34. Other Pre-specified Outcome

Title	Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both serious and non-serious adverse events.
Time Frame	From initiation of treatment up to follow-up period (up to 4 years)

Outcome Measure Data

Analysis Population Description
Safety analysis population included all enrolled participants who received at least 1 dose of Crizotinib on Cycle 1, Day 1.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	11	15	20	10	16	16
AE	9 81.8%	14 93.3%	15 75%	6 60%	11 68.8%	11 68.8%
SAE	0 0%	3 20%	0 0%	0 0%	0 0%	0 0%

35. Other Pre-specified Outcome

Title	Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities
Description	Anemia(grade[g]1:Less than[<] Lower limit of normal[LLN] to 10gram per[/] deciliter[g/dL],g2:<10 to 8g/dL,g3:<8g/dL,g4:lifethreatening);platelet (g1:<LLN to 7510^3/millimeter[mm]^3,g2:<7510^3/mm^3 to 5010^3/mm^3,g3:<5010^3/mm^3 to 2510^3/mm^3,g4:<2510^3/mm^3);lymphopenia(g1:<LLN to 810^2/mm^3,g2:<810^2 to 510^2/mm^3,g3:<510^2 to 210^2/mm^3,g4:<210^2/mm^3);neutrophil (Absolute)(g1:<LLN to 1510^2/mm^3,g2:<1510^2 to 1010^2/mm^3,g3:<1010^2 to 510^2/mm^3,g4:<510^2/mm^3);white blood cell count(g1:<LLN to 310^3/mm^3,g2:<310^3 to 210^3/mm^3,g3:<210^3 to 110^3/mm^3,g4:<110^3/mm^3);hemoglobin(g1:increase in hemoglobin level>0 to 2 g/dL above ULN or above baseline if baseline is above ULN,g2:increase in hemoglobin level>2 to 4g/dL above ULN or above baseline if baseline is above ULN,g3:increase in hemoglobin level>4 g/dL above ULN or above baseline if baseline is above ULN). Only categories with atleast 1 participant with abnormality are reported in this outcome measure.
Time Frame	Baseline up to end of treatment (up to 728 days)

Outcome Measure Data

Analysis Population Description
Safety analysis population included all enrolled participants who received at least 1 dose of Crizotinib on Cycle 1, Day 1.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	11	15	20	10	16	16
Anemia: Grade 1	4 36.4%	7 46.7%	9 45%	9 90%	7 43.8%	8 50%
Anemia: Grade 2	4 36.4%	7 46.7%	4 20%	1 10%	5 31.3%	5 31.3%
Anemia: Grade 3	1 9.1%	1 6.7%	3 15%	0 0%	1 6.3%	1 6.3%
Hemoglobin Increased: Grade 1	0 0%	0 0%	1 5%	0 0%	0 0%	0 0%
Lymphopenia: Grade 1	2 18.2%	2 13.3%	5 25%	2 20%	0 0%	1 6.3%
Lymphopenia: Grade 2	3 27.3%	7 46.7%	4 20%	6 60%	9 56.3%	7 43.8%
Lymphopenia: Grade 3	1 9.1%	1 6.7%	3 15%	2 20%	2 12.5%	4 25%
Lymphopenia: Grade 4	0 0%	0 0%	0 0%	0 0%	2 12.5%	0 0%
Neutrophils (Absolute): Grade 1	0 0%	0 0%	1 5%	2 20%	1 6.3%	2 12.5%
Neutrophils (Absolute): Grade 2	3 27.3%	1 6.7%	2 10%	0 0%	3 18.8%	0 0%
Neutrophils (Absolute): Grade 3	0 0%	0 0%	1 5%	0 0%	1 6.3%	3 18.8%
Platelets: Grade 1	0 0%	2 13.3%	4 20%	2 20%	8 50%	3 18.8%
Platelets: Grade 2	0 0%	0 0%	1 5%	0 0%	2 12.5%	2 12.5%
Platelets: Grade 3	0 0%	0 0%	2 10%	3 30%	2 12.5%	5 31.3%
White Blood Cells: Grade 1	2 18.2%	3 20%	4 20%	2 20%	2 12.5%	1 6.3%
White Blood Cells: Grade 2	1 9.1%	1 6.7%	3 15%	2 20%	3 18.8%	3 18.8%
White Blood Cells: Grade 3	0 0%	0 0%	0 0%	0 0%	1 6.3%	3 18.8%

36. Other Pre-specified Outcome

Title	Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities
Description	ALT/AST(grade[g]1:>ULN-3ULN,g2:>3-5ULN,g3:>5-20ULN,g4:>20ULN);AP(g1:>ULN-2.5ULN,g2:>2.5-5ULN,g3:>5-20ULN,g4:>20ULN);CR(g1:>ULN-1.5ULN,g2:>1.5-3ULN,g3:>3-6ULN,g4:>6ULN);hyperglycemia(g1:>ULN-160mg/dL,g2:>160-250mg/dL,g3:>250-500mg/dL,g4:>500mg/dL);bilirubin(total)(g1:>ULN-1.5ULN,g2:>1.5-3ULN,g3:>3-10ULN,g4:>10ULN);hypoglycemia(g1:<LLN-55mg/dL,g2:<55-40mg/dL,g3:<40-30mg/dL,g4:<30mg/dL);hyperkalemia(g1:>ULN-5.5mmol/L,g2:>5.5-6mmol/L,g3:>6-7mmol/L,g4:>7mmol/L);hypokalemia(g1:<LLN-3mmol/L,g2:<LLN-3mmol/L,g3:<3-2.5mmol/L,g4:<2.5mmol/L);hypermagnesemia(g1:>ULN-3mg/dL,g3:>3-8mg/dL,g4:>8mg/dL);hypocalcemia(g1:<LLN-8mg/dL,g2:<8-7mg/dL,g3:<7-6mg/dL,g4:<6mg/dL);hypomagnesemia(g1:<LLN-1.2mg/dL,g2:<1.2-0.9mg/dL,g3:<0.9-0.7mg/dL,g4:<0.7mg/dL);hyponatremia(g1:<LLN-130mmol/L,g3:<130-120mmol/L,g4:<120mmol/L);hypoalbuminemia(g1:<LLN-3g/dL,g2:<3-2g/dL,g3:<2g/dL,g4:lifethreatening);hypophosphatemia(g1:<LLN-2.5mg/dL,g2:<2.5-2mg/dL,g3:<2-1mg/dL,g4:<1mg/dL).Participant>=1abnormality given.
Time Frame	Baseline up to end of treatment (up to 728 days)

Outcome Measure Data

Analysis Population Description
Safety analysis population included all enrolled participants who received at least 1 dose of Crizotinib on Cycle 1, Day 1.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	11	15	20	10	16	16
Alanine aminotransferase (ALT): Grade 1	8 72.7%	3 20%	12 60%	6 60%	12 75%	9 56.3%
ALT: Grade 2	0 0%	0 0%	5 25%	2 20%	3 18.8%	5 31.3%
ALT: Grade 3	0 0%	0 0%	0 0%	1 10%	1 6.3%	0 0%
Alkaline phosphatase(AP): Grade 1	4 36.4%	7 46.7%	8 40%	4 40%	7 43.8%	5 31.3%
Alkaline phosphatase: Grade 2	2 18.2%	1 6.7%	5 25%	3 30%	4 25%	4 25%
Alkaline phosphatase: Grade 3	0 0%	1 6.7%	3 15%	3 30%	4 25%	6 37.5%
AST:Grade 1	6 54.5%	7 46.7%	8 40%	5 50%	4 25%	4 25%
AST: Grade 2	1 9.1%	0 0%	7 35%	0 0%	7 43.8%	3 18.8%
AST: Grade 3	0 0%	1 6.7%	3 15%	5 50%	5 31.3%	7 43.8%
AST: Grade 4	0 0%	0 0%	0 0%	0 0%	0 0%	2 12.5%
Bilirubin (total): Grade 1	1 9.1%	0 0%	2 10%	0 0%	0 0%	0 0%
Bilirubin (total): Grade 2	1 9.1%	0 0%	3 15%	1 10%	7 43.8%	0 0%
Bilirubin (total): Grade 3	0 0%	0 0%	2 10%	5 50%	8 50%	10 62.5%
Bilirubin (total): Grade 4	0 0%	0 0%	2 10%	3 30%	1 6.3%	6 37.5%
Creatinine (CR): Grade 1	9 81.8%	11 73.3%	8 40%	6 60%	6 37.5%	10 62.5%
CR: Grade 2	2 18.2%	4 26.7%	7 35%	3 30%	8 50%	5 31.3%
CR: Grade 3	0 0%	0 0%	1 5%	0 0%	1 6.3%	1 6.3%
Hyperglycemia: Grade 1	5 45.5%	8 53.3%	10 50%	8 80%	5 31.3%	8 50%
Hyperglycemia: Grade 2	1 9.1%	2 13.3%	5 25%	0 0%	4 25%	2 12.5%
Hyperglycemia: Grade 3	0 0%	1 6.7%	1 5%	0 0%	0 0%	4 25%
Hyperkalemia: Grade 1	2 18.2%	1 6.7%	4 20%	2 20%	3 18.8%	1 6.3%
Hyperkalemia: Grade 2	0 0%	0 0%	1 5%	0 0%	0 0%	0 0%
Hyperkalemia: Grade 3	0 0%	0 0%	1 5%	0 0%	1 6.3%	0 0%
Hypermagnesemia: Grade 1	1 9.1%	1 6.7%	4 20%	0 0%	2 12.5%	3 18.8%
Hypoalbuminemia: Grade 1	5 45.5%	4 26.7%	2 10%	1 10%	0 0%	0 0%
Hypoalbuminemia: Grade 2	5 45.5%	10 66.7%	9 45%	8 80%	14 87.5%	8 50%
Hypoalbuminemia: Grade 3	0 0%	0 0%	3 15%	1 10%	2 12.5%	7 43.8%
Hypocalcemia: Grade 1	5 45.5%	11 73.3%	5 25%	3 30%	4 25%	7 43.8%
Hypocalcemia: Grade 2	3 27.3%	1 6.7%	9 45%	4 40%	9 56.3%	9 56.3%
Hypoglycemia: Grade 1	0 0%	0 0%	2 10%	0 0%	2 12.5%	2 12.5%
Hypokalemia: Grade 1	4 36.4%	1 6.7%	5 25%	0 0%	5 31.3%	4 25%
Hypokalemia: Grade 3	0 0%	0 0%	0 0%	1 10%	0 0%	0 0%
Hypomagnesemia: Grade 1	0 0%	2 13.3%	5 25%	3 30%	4 25%	6 37.5%
Hyponatremia: Grade 1	5 45.5%	5 33.3%	4 20%	5 50%	7 43.8%	8 50%
Hyponatremia: Grade 3	1 9.1%	4 26.7%	7 35%	5 50%	7 43.8%	7 43.8%
Hypophosphatemia: Grade 1	0 0%	3 20%	1 5%	0 0%	0 0%	1 6.3%
Hypophosphatemia: Grade 2	1 9.1%	2 13.3%	3 15%	3 30%	3 18.8%	3 18.8%
Hypophosphatemia: Grade 3	2 18.2%	0 0%	1 5%	1 10%	3 18.8%	1 6.3%

37. Other Pre-specified Outcome

Title	Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Description	Criteria for abnormal value of ECG parameters: maximum increase from baseline (IFB) in QT interval using Fridericia's correction (QTcF)/QT interval using Bazett's correction (QTcB) range from less than (<)30 millisecond (msec), 30 to <60, greater than or equal to (>=)60 msec; maximum post-dose QTcF/QTcB ranges from <450 msec, 450 to <480 msec, 480 to <500, and >=500 msec; PR interval: >=50 percent (%) increase when baseline <200 msec; or increase >=25% when baseline less than or equal to (<=)200 msec; QRS interval: >=50% increase when baseline <100 msec; >=25% increase when baseline >=100 msec. Only categories which included atleast 1 participant with abnormality are reported in this outcome measure.
Time Frame	Baseline up to end of treatment (up to 728 days)

Outcome Measure Data

Analysis Population Description
Safety analysis population included all enrolled participants who received at least 1 dose of Crizotinib on Cycle 1, Day 1.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	11	15	20	10	16	16
Maximum Post-dose QTCF Interval: <450 msec	9 81.8%	13 86.7%	13 65%	8 80%	11 68.8%	6 37.5%
Maximum Post-dose QTCF Interval: 450 to <480 msec	1 9.1%	2 13.3%	6 30%	1 10%	5 31.3%	9 56.3%
Maximum Post-dose QTCF Interval: 480 to <500 msec	1 9.1%	0 0%	0 0%	1 10%	0 0%	1 6.3%
Maximum Post-dose QTCF Interval: >=500 msec	0 0%	0 0%	1 5%	0 0%	0 0%	0 0%
Maximum Post-dose QTCB Interval: <450 msec	10 90.9%	13 86.7%	12 60%	7 70%	11 68.8%	5 31.3%
Maximum Post-dose QTCB Interval: 450 to <480 msec	0 0%	2 13.3%	7 35%	2 20%	5 31.3%	8 50%
Maximum Post-dose QTCB Interval: 480 to <500 msec	1 9.1%	0 0%	0 0%	1 10%	0 0%	1 6.3%
Maximum Post-dose QTCB Interval: >=500 msec	0 0%	0 0%	1 5%	0 0%	0 0%	2 12.5%
Maximum QTCF Interval IFB: <30 msec	7 63.6%	12 80%	11 55%	7 70%	7 43.8%	8 50%
Maximum QTCF Interval IFB: 30 to 60 msec	2 18.2%	1 6.7%	1 5%	0 0%	4 25%	1 6.3%
Maximum QTCF IFB: >=60 msec	0 0%	0 0%	0 0%	1 10%	0 0%	1 6.3%
Maximum QTCB Interval IFB: <30 msec	7 63.6%	10 66.7%	8 40%	5 50%	7 43.8%	7 43.8%
Maximum QTCB Interval IFB: 30 to 60 msec	0 0%	1 6.7%	0 0%	1 10%	1 6.3%	1 6.3%
Maximum QTCB Interval IFB: >=60 msec	0 0%	0 0%	0 0%	1 10%	0 0%	1 6.3%
Maximum PR Interval IFB: >=50%	0 0%	1 6.7%	0 0%	0 0%	0 0%	0 0%
Maximum PR Interval IFB, Other Than: >=25 or 50%	10 90.9%	14 93.3%	19 95%	10 100%	15 93.8%	16 100%
Maximum QRS Interval IFB, Other Than: >=25 or 50%	11 100%	15 100%	20 100%	10 100%	16 100%	16 100%

38. Other Pre-specified Outcome

Title	Number of Participants With Abnormal Fundoscopy Examination Findings
Description	Fundoscopy examination included an examination of the vitreous body, retina macula, retina non-macula, optic nerve head, optic disc notching and fundus using the category of the examination status (normal, mild, moderate, or severe). In this outcome measure, number of participants with abnormal fundoscopy values identified by investigator were reported.
Time Frame	Baseline up to end of treatment (up to 728 days)

Outcome Measure Data

Analysis Population Description
Safety analysis population included all enrolled participants who received at least 1 dose of Crizotinib on Cycle 1, Day 1.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	11	15	20	10	16	16
Right Eye, Retina Macula: Mild Abnormality	0 0%	0 0%	1 5%	0 0%	0 0%	0 0%
Right Eye, Retina Non-Macula: Mild Abnormality	1 9.1%	0 0%	0 0%	0 0%	0 0%	0 0%
Right Eye, Optic Disc Notching: Mild Abnormality	1 9.1%	1 6.7%	0 0%	0 0%	0 0%	0 0%
Right Eye, Fundus: Mild Abnormality	0 0%	0 0%	1 5%	0 0%	0 0%	0 0%
Right Eye, Vitreous Body: Mild Abnormality	0 0%	0 0%	0 0%	1 10%	0 0%	0 0%
Left Eye, Retina Non-Macula: Mild Abnormality	1 9.1%	0 0%	0 0%	0 0%	1 6.3%	0 0%
Left Eye, Vitreous Body: Mild Abnormality	1 9.1%	0 0%	0 0%	1 10%	0 0%	0 0%
Left Eye, Fundus: Mild Abnormality	0 0%	0 0%	1 5%	0 0%	0 0%	0 0%
Left Eye, Retina Macula: Mild Abnormality	0 0%	0 0%	1 5%	0 0%	0 0%	0 0%
Left Eye, Optic Disc Notching: Mild Abnormality	1 9.1%	0 0%	0 0%	0 0%	0 0%	0 0%

39. Other Pre-specified Outcome

Title	Objective Response Rate (ORR)
Description	ORR was defined as percentage of participants with confirmed complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumors (RECIST) version 1.1. In case of target lesions CR was defined as the disappearance of all target lesions and in case nodal disease included in the sum of target lesions. The nodes decreased to normal size (<10 mm). In case of non-target lesions disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Confirmed responses were those who persisted on repeat imaging study at least 4 weeks after the initial documentation of response.
Time Frame	Baseline, every 8 weeks until disease progression or unacceptable toxicity up to end of treatment (up to 728 days)

Outcome Measure Data

Analysis Population Description
Response-evaluable population was defined as all participants in the safety analysis population who had an adequate baseline tumor assessment.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	11	15	20	10	16	16
Number (95% Confidence Interval) [percentage of participants]	9.1 82.7%	0 0%	5.0 25%	0 0%	6.3 39.4%	0 0%

40. Other Pre-specified Outcome

Title	Duration of Response (DR)
Description	DR was defined as the time from date of first documentation of CR or PR to first documentation of objective tumor progression or death due to any cause, whichever occurred first. In case of target lesions CR was defined as the disappearance of all target lesions and in case nodal disease included in the sum of target lesions. The nodes decreased to normal size (<10 mm). In case of non-target lesions disappearance of all non-target lesions and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Objective tumor progression as per RECIST version 1.1 was defined as >=20% increase in sum of diameters of target lesions taking as a reference smallest sum of diameters recorded since treatment started, or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. DR was estimated using Kaplan-Meier method.
Time Frame	Baseline, every 8 weeks until disease progression or unacceptable toxicity up to end of treatment (up to 728 days)

Outcome Measure Data

Analysis Population Description
Response evaluable population. Here, 'N' signifies participants who were evaluable for this outcome measure. Data for normal hepatic function (200 mg), moderate (250 mg) and severe (250 mg) hepatic impairment arms was not estimable since no participants had achieved CR or PR in these reporting arms.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily	Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily	Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily	Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily	Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily	Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).	Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.	Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.	Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN	Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
Measure Participants	1	0	1	0	1	0
Median (95% Confidence Interval) [week]	NA	17.4	NA

Adverse Events

	Normal Hepatic Function: Crizotinib 250 mg Twice Daily		Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily		Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily		Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily		Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily		Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Time Frame
Adverse Event Reporting Description	Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.

Arm/Group Title	Normal Hepatic Function: Crizotinib 250 mg Twice Daily		Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily		Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily		Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily		Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily		Severe Hepatic Impairment Crizotinib 250 mg Once Daily
Arm/Group Description	Participants with normal hepatic function received Crizotinib 250 milligram (mg) capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and aspartate aminotransferase (AST) levels less than or equal to (<=) the upper limit of normal (ULN).		Participants with normal hepatic function received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles and dose could be increased to 250 mg twice daily after completion of pharmacokinetic (PK) assessment on Cycle 2 Day 1 based on their tolerability. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Normal hepatic function was defined as total bilirubin and AST levels <=ULN.		Participants with mild hepatic impairment received Crizotinib 250 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Mild hepatic impairment was defined as total bilirubin level <=ULN and AST levels greater than (>) ULN or total bilirubin level > 1.0 to 1.5*ULN.		Participants with moderate hepatic impairment received Crizotinib 200 mg capsules, orally, twice daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN		Participants with moderate hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Moderate hepatic impairment was defined as total bilirubin level >1.5 to 3*ULN		Participants with severe hepatic impairment received Crizotinib 250 mg capsules, orally, once daily continuously in 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or withdrawal of consent occurred. Severe hepatic Impairment was defined as total bilirubin level >3*ULN.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/11 (27.3%)		4/15 (26.7%)		8/20 (40%)		5/10 (50%)		7/16 (43.8%)		9/16 (56.3%)
Serious Adverse Events
	Normal Hepatic Function: Crizotinib 250 mg Twice Daily		Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily		Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily		Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily		Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily		Severe Hepatic Impairment Crizotinib 250 mg Once Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/11 (63.6%)		8/15 (53.3%)		13/20 (65%)		6/10 (60%)		14/16 (87.5%)		14/16 (87.5%)
Blood and lymphatic system disorders
Anaemia	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Cardiac disorders
Atrial fibrillation	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		2/16 (12.5%)		0/16 (0%)
Gastrointestinal disorders
Abdominal pain	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		1/16 (6.3%)
Abdominal pain upper	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Anal fistula	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Ascites	0/11 (0%)		0/15 (0%)		0/20 (0%)		2/10 (20%)		2/16 (12.5%)		4/16 (25%)
Diarrhoea	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Gastrointestinal haemorrhage	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Nausea	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Oesophagitis	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Proctalgia	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Small intestinal obstruction	0/11 (0%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		1/16 (6.3%)		0/16 (0%)
Upper gastrointestinal haemorrhage	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Vomiting	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Intra-abdominal haemorrhage	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
General disorders
Asthenia	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Disease progression	2/11 (18.2%)		2/15 (13.3%)		4/20 (20%)		5/10 (50%)		4/16 (25%)		6/16 (37.5%)
Oedema	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Oedema peripheral	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Pyrexia	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Hepatobiliary disorders
Cholecystitis	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Hepatic failure	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		2/16 (12.5%)		0/16 (0%)
Hyperbilirubinaemia	0/11 (0%)		0/15 (0%)		1/20 (5%)		1/10 (10%)		0/16 (0%)		0/16 (0%)
Infections and infestations
Atypical pneumonia	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Gastroenteritis	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Meningitis bacterial	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Peritonitis	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Pneumonia	0/11 (0%)		1/15 (6.7%)		1/20 (5%)		0/10 (0%)		1/16 (6.3%)		2/16 (12.5%)
Sepsis	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Septic shock	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Urinary tract infection	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Injury, poisoning and procedural complications
Humerus fracture	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Pelvic fracture	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Metabolism and nutrition disorders
Dehydration	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Fluid overload	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Hyperammonaemia	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Hyperuricaemia	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Hypokalaemia	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Hyponatraemia	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Nervous system disorders
Aphasia	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Encephalopathy	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Generalised tonic-clonic seizure	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Haemorrhagic stroke	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Hepatic encephalopathy	0/11 (0%)		0/15 (0%)		1/20 (5%)		2/10 (20%)		2/16 (12.5%)		2/16 (12.5%)
Psychiatric disorders
Confusional state	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		2/16 (12.5%)		0/16 (0%)
Mental status changes	0/11 (0%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		1/16 (6.3%)		0/16 (0%)
Renal and urinary disorders
Acute kidney injury	0/11 (0%)		0/15 (0%)		2/20 (10%)		0/10 (0%)		1/16 (6.3%)		1/16 (6.3%)
Renal failure	0/11 (0%)		0/15 (0%)		2/20 (10%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Urinary retention	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	0/11 (0%)		0/15 (0%)		2/20 (10%)		1/10 (10%)		1/16 (6.3%)		0/16 (0%)
Dyspnoea exertional	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Pleural effusion	0/11 (0%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		2/16 (12.5%)		0/16 (0%)
Pneumonitis	0/11 (0%)		2/15 (13.3%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Pulmonary embolism	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Respiratory failure	0/11 (0%)		1/15 (6.7%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Surgical and medical procedures
Wound drainage	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Vascular disorders
Deep vein thrombosis	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Hypotension	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Normal Hepatic Function: Crizotinib 250 mg Twice Daily		Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily		Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily		Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily		Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily		Severe Hepatic Impairment Crizotinib 250 mg Once Daily
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/11 (100%)		15/15 (100%)		20/20 (100%)		9/10 (90%)		16/16 (100%)		16/16 (100%)
Blood and lymphatic system disorders
Anaemia	3/11 (27.3%)		5/15 (33.3%)		6/20 (30%)		2/10 (20%)		5/16 (31.3%)		3/16 (18.8%)
Coagulopathy	0/11 (0%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		0/16 (0%)		0/16 (0%)
Neutropenia	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		1/16 (6.3%)
Thrombocytopenia	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Cardiac disorders
Bradycardia	1/11 (9.1%)		2/15 (13.3%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Right ventricular failure	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Sinus bradycardia	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Eye disorders
Halo vision	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Photophobia	0/11 (0%)		2/15 (13.3%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Photopsia	2/11 (18.2%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Vision blurred	4/11 (36.4%)		1/15 (6.7%)		2/20 (10%)		3/10 (30%)		2/16 (12.5%)		0/16 (0%)
Visual impairment	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Vitreous floaters	2/11 (18.2%)		0/15 (0%)		2/20 (10%)		3/10 (30%)		3/16 (18.8%)		1/16 (6.3%)
Gastrointestinal disorders
Abdominal distension	3/11 (27.3%)		0/15 (0%)		2/20 (10%)		1/10 (10%)		2/16 (12.5%)		1/16 (6.3%)
Abdominal pain	1/11 (9.1%)		0/15 (0%)		5/20 (25%)		2/10 (20%)		1/16 (6.3%)		4/16 (25%)
Abdominal pain upper	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Constipation	6/11 (54.5%)		2/15 (13.3%)		4/20 (20%)		1/10 (10%)		4/16 (25%)		2/16 (12.5%)
Ascites	0/11 (0%)		0/15 (0%)		0/20 (0%)		3/10 (30%)		6/16 (37.5%)		6/16 (37.5%)
Diarrhoea	7/11 (63.6%)		4/15 (26.7%)		5/20 (25%)		1/10 (10%)		1/16 (6.3%)		1/16 (6.3%)
Dry mouth	1/11 (9.1%)		0/15 (0%)		1/20 (5%)		1/10 (10%)		3/16 (18.8%)		1/16 (6.3%)
Dyspepsia	3/11 (27.3%)		2/15 (13.3%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		1/16 (6.3%)
Dysphagia	2/11 (18.2%)		1/15 (6.7%)		1/20 (5%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Eructation	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Gastrointestinal haemorrhage	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Gastrooesophageal reflux disease	1/11 (9.1%)		2/15 (13.3%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Haematochezia	1/11 (9.1%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Nausea	7/11 (63.6%)		8/15 (53.3%)		11/20 (55%)		2/10 (20%)		7/16 (43.8%)		6/16 (37.5%)
Odynophagia	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Oesophagitis	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Proctalgia	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Rectal haemorrhage	0/11 (0%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		0/16 (0%)		0/16 (0%)
Vomiting	4/11 (36.4%)		8/15 (53.3%)		6/20 (30%)		2/10 (20%)		9/16 (56.3%)		3/16 (18.8%)
Aphthous ulcer	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
General disorders
Asthenia	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Chest discomfort	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Chest pain	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Chills	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Disease progression	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Face oedema	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		0/16 (0%)		0/16 (0%)
Fatigue	4/11 (36.4%)		6/15 (40%)		4/20 (20%)		5/10 (50%)		8/16 (50%)		7/16 (43.8%)
General physical health deterioration	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Malaise	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Mucosal inflammation	0/11 (0%)		1/15 (6.7%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Oedema	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		3/16 (18.8%)		0/16 (0%)
Pain	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		1/16 (6.3%)		0/16 (0%)
Pyrexia	0/11 (0%)		3/15 (20%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Oedema peripheral	4/11 (36.4%)		2/15 (13.3%)		3/20 (15%)		3/10 (30%)		5/16 (31.3%)		3/16 (18.8%)
Hepatobiliary disorders
Hyperbilirubinaemia	0/11 (0%)		0/15 (0%)		4/20 (20%)		2/10 (20%)		8/16 (50%)		0/16 (0%)
Infections and infestations
Body tinea	0/11 (0%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		0/16 (0%)		0/16 (0%)
Candida infection	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Conjunctivitis	0/11 (0%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		0/16 (0%)		0/16 (0%)
Influenza	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Pneumonia	0/11 (0%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		1/16 (6.3%)		0/16 (0%)
Respiratory tract infection	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Upper respiratory tract infection	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Urinary tract infection	1/11 (9.1%)		1/15 (6.7%)		3/20 (15%)		1/10 (10%)		1/16 (6.3%)		1/16 (6.3%)
Injury, poisoning and procedural complications
Fall	3/11 (27.3%)		3/15 (20%)		1/20 (5%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Road traffic accident	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Investigations
Activated partial thromboplastin time prolonged	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Alanine aminotransferase increased	3/11 (27.3%)		1/15 (6.7%)		6/20 (30%)		1/10 (10%)		2/16 (12.5%)		4/16 (25%)
Ammonia increased	0/11 (0%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		0/16 (0%)		0/16 (0%)
Aspartate aminotransferase increased	3/11 (27.3%)		4/15 (26.7%)		7/20 (35%)		2/10 (20%)		5/16 (31.3%)		5/16 (31.3%)
Blood albumin decreased	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Blood alkaline phosphatase increased	2/11 (18.2%)		2/15 (13.3%)		2/20 (10%)		1/10 (10%)		2/16 (12.5%)		2/16 (12.5%)
Blood bilirubin increased	0/11 (0%)		0/15 (0%)		2/20 (10%)		5/10 (50%)		1/16 (6.3%)		1/16 (6.3%)
Blood creatinine increased	5/11 (45.5%)		4/15 (26.7%)		5/20 (25%)		4/10 (40%)		3/16 (18.8%)		3/16 (18.8%)
Blood lactate dehydrogenase increased	0/11 (0%)		1/15 (6.7%)		1/20 (5%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Blood phosphorus decreased	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Heart rate decreased	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
International normalised ratio increased	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		0/16 (0%)		0/16 (0%)
Neutrophil count decreased	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		3/16 (18.8%)
Platelet count decreased	0/11 (0%)		0/15 (0%)		1/20 (5%)		1/10 (10%)		1/16 (6.3%)		3/16 (18.8%)
Transaminases increased	0/11 (0%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		1/16 (6.3%)		0/16 (0%)
Weight decreased	0/11 (0%)		1/15 (6.7%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Weight increased	0/11 (0%)		0/15 (0%)		1/20 (5%)		2/10 (20%)		1/16 (6.3%)		1/16 (6.3%)
White blood cell count decreased	0/11 (0%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		1/16 (6.3%)		3/16 (18.8%)
Metabolism and nutrition disorders
Abnormal loss of weight	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Cachexia	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Decreased appetite	4/11 (36.4%)		4/15 (26.7%)		5/20 (25%)		2/10 (20%)		6/16 (37.5%)		2/16 (12.5%)
Dehydration	0/11 (0%)		3/15 (20%)		1/20 (5%)		0/10 (0%)		3/16 (18.8%)		2/16 (12.5%)
Food intolerance	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Hypoalbuminaemia	1/11 (9.1%)		2/15 (13.3%)		0/20 (0%)		0/10 (0%)		2/16 (12.5%)		0/16 (0%)
Hypocalcaemia	1/11 (9.1%)		1/15 (6.7%)		1/20 (5%)		0/10 (0%)		1/16 (6.3%)		1/16 (6.3%)
Hypokalaemia	1/11 (9.1%)		0/15 (0%)		2/20 (10%)		2/10 (20%)		1/16 (6.3%)		1/16 (6.3%)
Hypomagnesaemia	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Hyponatraemia	0/11 (0%)		6/15 (40%)		5/20 (25%)		6/10 (60%)		4/16 (25%)		6/16 (37.5%)
Hypophagia	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Hypophosphataemia	1/11 (9.1%)		2/15 (13.3%)		1/20 (5%)		4/10 (40%)		2/16 (12.5%)		2/16 (12.5%)
Metabolic acidosis	0/11 (0%)		0/15 (0%)		2/20 (10%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Hyperglycaemia	2/11 (18.2%)		2/15 (13.3%)		3/20 (15%)		3/10 (30%)		1/16 (6.3%)		3/16 (18.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/11 (27.3%)		0/15 (0%)		1/20 (5%)		1/10 (10%)		0/16 (0%)		1/16 (6.3%)
Arthritis	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Back pain	0/11 (0%)		2/15 (13.3%)		1/20 (5%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Flank pain	0/11 (0%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		0/16 (0%)		0/16 (0%)
Joint effusion	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Joint swelling	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Muscle spasms	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Muscular weakness	2/11 (18.2%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Musculoskeletal chest pain	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		1/10 (10%)		1/16 (6.3%)		0/16 (0%)
Musculoskeletal pain	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Myalgia	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		0/16 (0%)		0/16 (0%)
Neck pain	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Pain in extremity	2/11 (18.2%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Nervous system disorders
Aphasia	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Dizziness	1/11 (9.1%)		2/15 (13.3%)		1/20 (5%)		1/10 (10%)		4/16 (25%)		2/16 (12.5%)
Dysgeusia	3/11 (27.3%)		2/15 (13.3%)		4/20 (20%)		2/10 (20%)		1/16 (6.3%)		1/16 (6.3%)
Encephalopathy	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		2/16 (12.5%)
Headache	2/11 (18.2%)		1/15 (6.7%)		1/20 (5%)		1/10 (10%)		0/16 (0%)		3/16 (18.8%)
Hepatic encephalopathy	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		2/16 (12.5%)
Memory impairment	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Migraine	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Myoclonus	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Neuropathy peripheral	1/11 (9.1%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Paraesthesia	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		1/16 (6.3%)		1/16 (6.3%)
Visual perseveration	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Somnolence	0/11 (0%)		0/15 (0%)		2/20 (10%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Psychiatric disorders
Anxiety	1/11 (9.1%)		0/15 (0%)		2/20 (10%)		0/10 (0%)		2/16 (12.5%)		0/16 (0%)
Confusional state	0/11 (0%)		0/15 (0%)		1/20 (5%)		0/10 (0%)		1/16 (6.3%)		1/16 (6.3%)
Insomnia	1/11 (9.1%)		0/15 (0%)		3/20 (15%)		1/10 (10%)		0/16 (0%)		1/16 (6.3%)
Libido decreased	0/11 (0%)		0/15 (0%)		0/20 (0%)		1/10 (10%)		0/16 (0%)		0/16 (0%)
Mental status changes	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Renal and urinary disorders
Acute kidney injury	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		1/16 (6.3%)
Haematuria	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Hydronephrosis	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Proteinuria	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Reproductive system and breast disorders
Erectile dysfunction	0/7 (0%)		0/9 (0%)		0/13 (0%)		1/8 (12.5%)		1/10 (10%)		0/10 (0%)
Gynaecomastia	0/7 (0%)		0/9 (0%)		0/13 (0%)		1/8 (12.5%)		0/10 (0%)		0/10 (0%)
Ovarian cyst	1/4 (25%)		0/6 (0%)		0/7 (0%)		0/2 (0%)		0/6 (0%)		0/6 (0%)
Penile swelling	0/7 (0%)		0/9 (0%)		0/13 (0%)		1/8 (12.5%)		0/10 (0%)		0/10 (0%)
Scrotal oedema	1/7 (14.3%)		0/9 (0%)		0/13 (0%)		0/8 (0%)		0/10 (0%)		0/10 (0%)
Scrotal pain	1/7 (14.3%)		0/9 (0%)		0/13 (0%)		0/8 (0%)		0/10 (0%)		0/10 (0%)
Vaginal haemorrhage	0/4 (0%)		0/6 (0%)		0/7 (0%)		0/2 (0%)		0/6 (0%)		1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Cough	1/11 (9.1%)		2/15 (13.3%)		2/20 (10%)		1/10 (10%)		1/16 (6.3%)		2/16 (12.5%)
Dry throat	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Dyspnoea	1/11 (9.1%)		0/15 (0%)		1/20 (5%)		3/10 (30%)		1/16 (6.3%)		2/16 (12.5%)
Dyspnoea exertional	1/11 (9.1%)		0/15 (0%)		1/20 (5%)		1/10 (10%)		0/16 (0%)		0/16 (0%)
Epistaxis	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Oropharyngeal pain	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Pleural effusion	1/11 (9.1%)		0/15 (0%)		1/20 (5%)		1/10 (10%)		2/16 (12.5%)		1/16 (6.3%)
Pulmonary hypertension	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Skin and subcutaneous tissue disorders
Alopecia	1/11 (9.1%)		0/15 (0%)		1/20 (5%)		1/10 (10%)		0/16 (0%)		1/16 (6.3%)
Dry skin	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		2/10 (20%)		0/16 (0%)		1/16 (6.3%)
Photosensitivity reaction	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		1/16 (6.3%)
Pruritus	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		2/10 (20%)		0/16 (0%)		1/16 (6.3%)
Rash	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Rash macular	0/11 (0%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Skin lesion	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Vascular disorders
Deep vein thrombosis	1/11 (9.1%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)
Flushing	0/11 (0%)		0/15 (0%)		0/20 (0%)		2/10 (20%)		0/16 (0%)		0/16 (0%)
Hypertension	0/11 (0%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		1/16 (6.3%)
Hypotension	1/11 (9.1%)		1/15 (6.7%)		0/20 (0%)		0/10 (0%)		1/16 (6.3%)		0/16 (0%)
Thrombophlebitis superficial	1/11 (9.1%)		0/15 (0%)		0/20 (0%)		0/10 (0%)		0/16 (0%)		0/16 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.

Results Point of Contact

Name/Title	Pfizer ClinicalTrials.gov Call Center
Organization	Pfizer, Inc.
Phone	1-800-718-1021
Email	ClinicalTrials.gov_Inquiries@pfizer.com

Responsible Party:

Pfizer

ClinicalTrials.gov Identifier:

NCT01576406

Other Study ID Numbers:

A8081012

First Posted:

Apr 12, 2012

Last Update Posted:

Oct 25, 2018

Last Verified:

Jan 1, 2018

Hepatic Impairment Study For Crizotinib In Advanced Cancer Patients

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Other Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Additional Information:

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Statistical Analysis 3

Statistical Analysis 4

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality