Advanced Cancer
Conditions
Keywords
crizotinib, xalkori, PF-02341066, hepatic impairment, pharmacokinetics, advanced cancer
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.
Interventions
DRUGcrizotinib
crizotinib 250 mg twice a day
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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: 1. 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. 2. The presence of liver lesion(s) (as defined in a.) with AFP ≥ 400 ng/mL. 3. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily 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). | 11 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily 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. | 15 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily 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. | 20 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily 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 | 10 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily 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 | 16 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily 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. | 16 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 3 | 4 | 8 | 5 | 7 | 9 |
| Overall Study | Lost to Follow-up | 1 | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Non-clinical trial supply of Crizotinib | 0 | 0 | 1 | 1 | 0 | 0 |
| Overall Study | Other | 0 | 0 | 2 | 2 | 0 | 0 |
| Overall Study | Withdrawal the consent | 2 | 2 | 5 | 1 | 1 | 3 |
Baseline characteristics
| Characteristic | 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 |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 57.7 years STANDARD_DEVIATION 15.64 | 62.9 years STANDARD_DEVIATION 10.35 | 61.2 years STANDARD_DEVIATION 10.14 | 59.2 years STANDARD_DEVIATION 8.85 | 60.3 years STANDARD_DEVIATION 7.87 | 59.0 years STANDARD_DEVIATION 6.04 | 60.3 years STANDARD_DEVIATION 9.77 |
| Sex: Female, Male Female | 4 Participants | 6 Participants | 7 Participants | 2 Participants | 6 Participants | 6 Participants | 31 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 13 Participants | 8 Participants | 10 Participants | 10 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 11 | 4 / 15 | 8 / 20 | 5 / 10 | 7 / 16 | 9 / 16 |
| other Total, other adverse events | 11 / 11 | 15 / 15 | 20 / 20 | 9 / 10 | 16 / 16 | 16 / 16 |
| serious Total, serious adverse events | 7 / 11 | 8 / 15 | 13 / 20 | 6 / 10 | 14 / 16 | 14 / 16 |
Outcome results
Primary
Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1 | 3552 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 48 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1 | 2712 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 66 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1 | 3238 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 73 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1 | 2305 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 83 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1 | 4057 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 58 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1 | 4596 nanogram*hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 63 |
Primary
Maximum Observed Plasma Concentration (Cmax) of Crizotinib: 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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 2 Day 1 | 375.1 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 50 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 2 Day 1 | 283.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 65 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 2 Day 1 | 342.1 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 68 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 2 Day 1 | 152.9 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 58 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 2 Day 1 | 408.3 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 56 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 2 Day 1 | 272.4 nanogram per milliliter (ng/mL) | Geometric Coefficient of Variation 29 |
Comparison: Confidence interval (CI): Geometric mean ratio and 90 percent (%) CI were derived from analysis of variance (ANOVA) model.90% CI: [57.47, 144.72]
Comparison: CI: Geometric mean ratio and 90% CI were derived from ANOVA model.90% CI: [89.11, 232.12]
Comparison: CI: Geometric mean ratio and 90% CI were derived from ANOVA model.90% CI: [70.13, 168.99]
Comparison: CI: Geometric mean ratio and 90% CI were derived from ANOVA model.90% CI: [49.07, 107.5]
Secondary
Apparent Oral Clearance (CL/F) of Crizotinib: Cycle 2 Day 1
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Apparent Oral Clearance (CL/F) of Crizotinib: Cycle 2 Day 1 | 70.39 Liter/hour | Geometric Coefficient of Variation 48 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Apparent Oral Clearance (CL/F) of Crizotinib: Cycle 2 Day 1 | 73.79 Liter/hour | Geometric Coefficient of Variation 66 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Apparent Oral Clearance (CL/F) of Crizotinib: Cycle 2 Day 1 | 77.21 Liter/hour | Geometric Coefficient of Variation 73 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Apparent Oral Clearance (CL/F) of Crizotinib: Cycle 2 Day 1 | 108.5 Liter/hour | Geometric Coefficient of Variation 83 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Apparent Oral Clearance (CL/F) of Crizotinib: Cycle 2 Day 1 | 49.26 Liter/hour | Geometric Coefficient of Variation 58 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Apparent Oral Clearance (CL/F) of Crizotinib: Cycle 2 Day 1 | 54.36 Liter/hour | Geometric Coefficient of Variation 63 |
Secondary
Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1 | 1087 ng*hr/mL | Geometric Coefficient of Variation 43 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1 | 717.4 ng*hr/mL | Geometric Coefficient of Variation 81 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1 | 480.3 ng*hr/mL | Geometric Coefficient of Variation 168 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1 | 200.0 ng*hr/mL | Geometric Coefficient of Variation 48 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1 | 391.8 ng*hr/mL | Geometric Coefficient of Variation 118 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1 | 434.0 ng*hr/mL | Geometric Coefficient of Variation 96 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast) of PF-06260182: Cycle 1 Day 1
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
Population: PK evaluable set. Here, 'N' signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast) of PF-06260182: Cycle 1 Day 1 | 272.4 ng*hr/mL | Geometric Coefficient of Variation 80 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast) of PF-06260182: Cycle 1 Day 1 | 166.5 ng*hr/mL | Geometric Coefficient of Variation 31 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast) of PF-06260182: Cycle 1 Day 1 | 90.71 ng*hr/mL | Geometric Coefficient of Variation 153 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast) of PF-06260182: Cycle 1 Day 1 | 64.90 ng*hr/mL | Geometric Coefficient of Variation 103 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast) of PF-06260182: Cycle 1 Day 1 | 53.36 ng*hr/mL | Geometric Coefficient of Variation 139 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast) of PF-06260182: Cycle 1 Day 1 | 59.61 ng*hr/mL | Geometric Coefficient of Variation 81 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of Crizotinib: 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
Population: PK evaluable set. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of Crizotinib: Cycle 1 Day 1 | 732.3 ng*hr/mL | Geometric Coefficient of Variation 84 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of Crizotinib: Cycle 1 Day 1 | 520.8 ng*hr/mL | Geometric Coefficient of Variation 49 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of Crizotinib: Cycle 1 Day 1 | 557.5 ng*hr/mL | Geometric Coefficient of Variation 78 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of Crizotinib: Cycle 1 Day 1 | 610.4 ng*hr/mL | Geometric Coefficient of Variation 128 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of Crizotinib: Cycle 1 Day 1 | 684.9 ng*hr/mL | Geometric Coefficient of Variation 89 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of Crizotinib: Cycle 1 Day 1 | 856.7 ng*hr/mL | Geometric Coefficient of Variation 57 |
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of Crizotinib: 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
Population: 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.
Secondary
Fraction of Unbound Crizotinib in Plasma: Cycle 2 Day 1
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Fraction of Unbound Crizotinib in Plasma: Cycle 2 Day 1 | 0.03624 ratio | Geometric Coefficient of Variation 26 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Fraction of Unbound Crizotinib in Plasma: Cycle 2 Day 1 | 0.03066 ratio | Geometric Coefficient of Variation 27 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Fraction of Unbound Crizotinib in Plasma: Cycle 2 Day 1 | 0.04315 ratio | Geometric Coefficient of Variation 31 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Fraction of Unbound Crizotinib in Plasma: Cycle 2 Day 1 | 0.05406 ratio | Geometric Coefficient of Variation 20 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Fraction of Unbound Crizotinib in Plasma: Cycle 2 Day 1 | 0.04152 ratio | Geometric Coefficient of Variation 34 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Fraction of Unbound Crizotinib in Plasma: Cycle 2 Day 1 | 0.03523 ratio | Geometric Coefficient of Variation 46 |
Secondary
Fraction of Unbound PF-06260182 in Plasma: Cycle 2 Day 1
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Fraction of Unbound PF-06260182 in Plasma: Cycle 2 Day 1 | 0.03797 ratio | Geometric Coefficient of Variation 11 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Fraction of Unbound PF-06260182 in Plasma: Cycle 2 Day 1 | 0.03822 ratio | Geometric Coefficient of Variation 16 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Fraction of Unbound PF-06260182 in Plasma: Cycle 2 Day 1 | 0.04857 ratio | Geometric Coefficient of Variation 16 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Fraction of Unbound PF-06260182 in Plasma: Cycle 2 Day 1 | 0.05788 ratio | Geometric Coefficient of Variation 22 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Fraction of Unbound PF-06260182 in Plasma: Cycle 2 Day 1 | 0.05031 ratio | Geometric Coefficient of Variation 10 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Fraction of Unbound PF-06260182 in Plasma: Cycle 2 Day 1 | 0.05177 ratio | Geometric Coefficient of Variation 13 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Crizotinib: 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
Population: PK evaluable set. Here, 'N' signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 1 Day 1 | 101.9 ng/mL | Geometric Coefficient of Variation 92 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 1 Day 1 | 84.52 ng/mL | Geometric Coefficient of Variation 67 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 1 Day 1 | 102.3 ng/mL | Geometric Coefficient of Variation 66 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 1 Day 1 | 57.74 ng/mL | Geometric Coefficient of Variation 112 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 1 Day 1 | 99.59 ng/mL | Geometric Coefficient of Variation 88 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 1 Day 1 | 90.69 ng/mL | Geometric Coefficient of Variation 63 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1
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
Population: PK evaluable set. Here, 'N' signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1 | 35.48 ng/mL | Geometric Coefficient of Variation 86 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1 | 24.12 ng/mL | Geometric Coefficient of Variation 33 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1 | 13.54 ng/mL | Geometric Coefficient of Variation 153 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1 | 4.869 ng/mL | Geometric Coefficient of Variation 95 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1 | 6.995 ng/mL | Geometric Coefficient of Variation 152 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1 | 4.088 ng/mL | Geometric Coefficient of Variation 88 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 108.5 ng/mL | Geometric Coefficient of Variation 43 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 73.47 ng/mL | Geometric Coefficient of Variation 76 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 50.34 ng/mL | Geometric Coefficient of Variation 164 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 12.43 ng/mL | Geometric Coefficient of Variation 55 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 39.32 ng/mL | Geometric Coefficient of Variation 120 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 25.15 ng/mL | Geometric Coefficient of Variation 110 |
Secondary
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
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | 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 | 0.2968 ratio | Geometric Coefficient of Variation 17 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | 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 | 0.2569 ratio | Geometric Coefficient of Variation 31 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | 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 | 0.1439 ratio | Geometric Coefficient of Variation 74 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | 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 | 0.08402 ratio | Geometric Coefficient of Variation 65 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | 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 | 0.09360 ratio | Geometric Coefficient of Variation 47 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | 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 | 0.09162 ratio | Geometric Coefficient of Variation 47 |
Secondary
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
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
Population: PK evaluable set. Here, 'N' signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | 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 | 0.3608 ratio | Geometric Coefficient of Variation 18 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | 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 | 0.3104 ratio | Geometric Coefficient of Variation 30 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | 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 | 0.1577 ratio | Geometric Coefficient of Variation 60 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | 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 | 0.1032 ratio | Geometric Coefficient of Variation 72 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | 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 | 0.07566 ratio | Geometric Coefficient of Variation 42 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | 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 | 0.06753 ratio | Geometric Coefficient of Variation 21 |
Secondary
Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1
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
Population: PK evaluable set. Here, 'N' signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1 | 0.3378 ratio | Geometric Coefficient of Variation 25 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1 | 0.2769 ratio | Geometric Coefficient of Variation 41 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1 | 0.1284 ratio | Geometric Coefficient of Variation 70 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1 | 0.08178 ratio | Geometric Coefficient of Variation 66 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1 | 0.06809 ratio | Geometric Coefficient of Variation 47 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 1 Day 1 | 0.04373 ratio | Geometric Coefficient of Variation 42 |
Secondary
Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 0.2804 ratio | Geometric Coefficient of Variation 19 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 0.2511 ratio | Geometric Coefficient of Variation 31 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 0.1428 ratio | Geometric Coefficient of Variation 73 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 0.07881 ratio | Geometric Coefficient of Variation 58 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 0.09337 ratio | Geometric Coefficient of Variation 49 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Metabolite Ratio for Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 0.08954 ratio | Geometric Coefficient of Variation 90 |
Secondary
Minimum Observed Plasma Concentration (Cmin) of Crizotinib: 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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Minimum Observed Plasma Concentration (Cmin) of Crizotinib: Cycle 2 Day 1 | 238.6 ng/mL | Geometric Coefficient of Variation 52 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Minimum Observed Plasma Concentration (Cmin) of Crizotinib: Cycle 2 Day 1 | 170.9 ng/mL | Geometric Coefficient of Variation 75 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Minimum Observed Plasma Concentration (Cmin) of Crizotinib: Cycle 2 Day 1 | 179.1 ng/mL | Geometric Coefficient of Variation 101 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Minimum Observed Plasma Concentration (Cmin) of Crizotinib: Cycle 2 Day 1 | 47.44 ng/mL | Geometric Coefficient of Variation 376 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Minimum Observed Plasma Concentration (Cmin) of Crizotinib: Cycle 2 Day 1 | 287.0 ng/mL | Geometric Coefficient of Variation 58 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Minimum Observed Plasma Concentration (Cmin) of Crizotinib: Cycle 2 Day 1 | 135.5 ng/mL | Geometric Coefficient of Variation 102 |
Secondary
Plasma Accumulation Ratio (Rac) of Crizotinib
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
Population: 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.
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib: 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
Population: PK evaluable set. Here, 'N' signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib: Cycle 1 Day 1 | 4.00 hour |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib: Cycle 1 Day 1 | 4.00 hour |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib: Cycle 1 Day 1 | 4.00 hour |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib: Cycle 1 Day 1 | 2.02 hour |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib: Cycle 1 Day 1 | 4.00 hour |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Crizotinib: Cycle 1 Day 1 | 3.00 hour |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 1 Day 1
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
Population: PK evaluable set. Here, 'N' signifies those participants who were evaluable for this measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 1 Day 1 | 6.04 hour |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 1 Day 1 | 4.00 hour |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 1 Day 1 | 4.00 hour |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 1 Day 1 | 6.08 hour |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 1 Day 1 | 8.00 hour |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 1 Day 1 | 7.00 hour |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 2 Day 1
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
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 2 Day 1 | 6.00 hour |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 2 Day 1 | 4.03 hour |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 2 Day 1 | 4.00 hour |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 2 Day 1 | 6.00 hour |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 2 Day 1 | 0 hour |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-06260182: Cycle 2 Day 1 | 6.69 hour |
Secondary
Unbound Area Under Plasma Concentration-Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Unbound Area Under Plasma Concentration-Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1 | 128.7 ng*hr/mL | Geometric Coefficient of Variation 38 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Unbound Area Under Plasma Concentration-Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1 | 83.08 ng*hr/mL | Geometric Coefficient of Variation 73 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Unbound Area Under Plasma Concentration-Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1 | 139.7 ng*hr/mL | Geometric Coefficient of Variation 94 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Unbound Area Under Plasma Concentration-Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1 | 124.6 ng*hr/mL | Geometric Coefficient of Variation 85 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Unbound Area Under Plasma Concentration-Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1 | 168.6 ng*hr/mL | Geometric Coefficient of Variation 59 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Unbound Area Under Plasma Concentration-Time Curve From Time Zero to End of Dosing Interval (AUCtau) of Crizotinib: Cycle 2 Day 1 | 161.9 ng*hr/mL | Geometric Coefficient of Variation 48 |
Secondary
Unbound Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Unbound Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1 | 41.26 ng*hr/mL | Geometric Coefficient of Variation 36 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Unbound Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1 | 27.40 ng*hr/mL | Geometric Coefficient of Variation 99 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Unbound Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1 | 23.35 ng*hr/mL | Geometric Coefficient of Variation 181 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Unbound Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1 | 11.56 ng*hr/mL | Geometric Coefficient of Variation 49 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Unbound Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1 | 19.71 ng*hr/mL | Geometric Coefficient of Variation 119 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Unbound Area Under Plasma Concentration Time Curve From Time Zero to End of Dosing Interval (AUCtau) of PF-06260182: Cycle 2 Day 1 | 22.49 ng*hr/mL | Geometric Coefficient of Variation 79 |
Secondary
Unbound Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUClast) of PF-06260182: Cycle 2 Day 1
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
Population: 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.
Secondary
Unbound Area Under the Plasma Concentration Time Curve From Time Zero to the Last Quantifiable Plasma Concentration (AUClast) of Crizotinib: Cycle 2 Day 1
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
Population: 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.
Secondary
Unbound Maximum Observed Plasma Concentration (Cmax) of Crizotinib: 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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Unbound Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 2 Day 1 | 13.59 ng/mL | Geometric Coefficient of Variation 41 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Unbound Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 2 Day 1 | 8.703 ng/mL | Geometric Coefficient of Variation 74 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Unbound Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 2 Day 1 | 14.77 ng/mL | Geometric Coefficient of Variation 93 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Unbound Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 2 Day 1 | 8.271 ng/mL | Geometric Coefficient of Variation 62 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Unbound Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 2 Day 1 | 16.96 ng/mL | Geometric Coefficient of Variation 56 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Unbound Maximum Observed Plasma Concentration (Cmax) of Crizotinib: Cycle 2 Day 1 | 9.608 ng/mL | Geometric Coefficient of Variation 34 |
Secondary
Unbound Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Unbound Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 4.119 ng/mL | Geometric Coefficient of Variation 36 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Unbound Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 2.806 ng/mL | Geometric Coefficient of Variation 94 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Unbound Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 2.445 ng/mL | Geometric Coefficient of Variation 178 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Unbound Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 0.7194 ng/mL | Geometric Coefficient of Variation 50 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Unbound Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 1.977 ng/mL | Geometric Coefficient of Variation 122 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Unbound Maximum Observed Plasma Concentration (Cmax) of PF-06260182: Cycle 2 Day 1 | 1.301 ng/mL | Geometric Coefficient of Variation 93 |
Other Pre-specified
Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: 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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: Cycle 2 Day 1 | 7107 ng*hr/mL | Geometric Coefficient of Variation 48 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: Cycle 2 Day 1 | 5422 ng*hr/mL | Geometric Coefficient of Variation 66 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: Cycle 2 Day 1 | 6476 ng*hr/mL | Geometric Coefficient of Variation 73 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: Cycle 2 Day 1 | 2305 ng*hr/mL | Geometric Coefficient of Variation 83 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: Cycle 2 Day 1 | 8108 ng*hr/mL | Geometric Coefficient of Variation 58 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: Cycle 2 Day 1 | 4596 ng*hr/mL | Geometric Coefficient of Variation 63 |
Comparison: CI: Geometric mean ratio and 90% CI were derived from ANOVA model.90% CI: [56.56, 146.79]
Comparison: CI: Geometric mean ratio and 90% CI were derived from ANOVA model.90% CI: [91.85, 243.46]
Comparison: CI: Geometric mean ratio and 90% CI were derived from ANOVA model.90% CI: [73.57, 176.89]
Comparison: CI: Geometric mean ratio and 90% CI were derived from ANOVA model.90% CI: [39.5, 105.89]
Other Pre-specified
Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1 | 2173 ng*hr/mL | Geometric Coefficient of Variation 43 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1 | 1435 ng*hr/mL | Geometric Coefficient of Variation 81 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1 | 961.2 ng*hr/mL | Geometric Coefficient of Variation 168 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1 | 200.0 ng*hr/mL | Geometric Coefficient of Variation 48 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1 | 784.0 ng*hr/mL | Geometric Coefficient of Variation 117 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1 | 434.0 ng*hr/mL | Geometric Coefficient of Variation 96 |
Other Pre-specified
Duration of Response (DR)
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)
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Duration of Response (DR) | NA week |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Duration of Response (DR) | 17.4 week |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Duration of Response (DR) | NA week |
Other Pre-specified
Number of Participants With Abnormal Electrocardiogram (ECG) Findings
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)
Population: Safety analysis population included all enrolled participants who received at least 1 dose of Crizotinib on Cycle 1, Day 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum PR Interval IFB, Other Than: >=25 or 50% | 10 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: >=500 msec | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: <450 msec | 9 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: >=60 msec | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: 450 to <480 msec | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: 450 to <480 msec | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: 30 to 60 msec | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: <450 msec | 10 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF IFB: >=60 msec | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum PR Interval IFB: >=50% | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: 30 to 60 msec | 2 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: >=500 msec | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: 480 to <500 msec | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: <30 msec | 7 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: 480 to <500 msec | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: <30 msec | 7 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QRS Interval IFB, Other Than: >=25 or 50% | 11 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: 450 to <480 msec | 2 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: <30 msec | 10 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: 30 to 60 msec | 1 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF IFB: >=60 msec | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: 480 to <500 msec | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: <450 msec | 13 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum PR Interval IFB, Other Than: >=25 or 50% | 14 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: >=500 msec | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum PR Interval IFB: >=50% | 1 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: <450 msec | 13 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QRS Interval IFB, Other Than: >=25 or 50% | 15 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: >=60 msec | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: 480 to <500 msec | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: 450 to <480 msec | 2 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: 30 to 60 msec | 1 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: >=500 msec | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: <30 msec | 12 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: 450 to <480 msec | 6 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: >=500 msec | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: 480 to <500 msec | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF IFB: >=60 msec | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: 480 to <500 msec | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: <30 msec | 8 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: 30 to 60 msec | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: 30 to 60 msec | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum PR Interval IFB, Other Than: >=25 or 50% | 19 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: <30 msec | 11 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: >=500 msec | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: <450 msec | 12 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: >=60 msec | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum PR Interval IFB: >=50% | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: <450 msec | 13 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: 450 to <480 msec | 7 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QRS Interval IFB, Other Than: >=25 or 50% | 20 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF IFB: >=60 msec | 1 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: <450 msec | 8 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: 450 to <480 msec | 1 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: 480 to <500 msec | 1 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: >=500 msec | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: <450 msec | 7 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: 450 to <480 msec | 2 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: 480 to <500 msec | 1 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: >=500 msec | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: <30 msec | 7 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: 30 to 60 msec | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: <30 msec | 5 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: 30 to 60 msec | 1 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: >=60 msec | 1 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum PR Interval IFB: >=50% | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum PR Interval IFB, Other Than: >=25 or 50% | 10 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QRS Interval IFB, Other Than: >=25 or 50% | 10 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: 30 to 60 msec | 1 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: >=500 msec | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: >=500 msec | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum PR Interval IFB: >=50% | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: <30 msec | 7 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: 450 to <480 msec | 5 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: 480 to <500 msec | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: 480 to <500 msec | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QRS Interval IFB, Other Than: >=25 or 50% | 16 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum PR Interval IFB, Other Than: >=25 or 50% | 15 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: <450 msec | 11 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: >=60 msec | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: 30 to 60 msec | 4 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF IFB: >=60 msec | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: 450 to <480 msec | 5 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: <450 msec | 11 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: <30 msec | 7 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: >=500 msec | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: <30 msec | 7 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: 480 to <500 msec | 1 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: <450 msec | 6 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: 30 to 60 msec | 1 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: 450 to <480 msec | 8 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: <450 msec | 5 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCB Interval IFB: >=60 msec | 1 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCB Interval: >=500 msec | 2 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QRS Interval IFB, Other Than: >=25 or 50% | 16 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum PR Interval IFB: >=50% | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: 480 to <500 msec | 1 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum Post-dose QTCF Interval: 450 to <480 msec | 9 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum PR Interval IFB, Other Than: >=25 or 50% | 16 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: 30 to 60 msec | 1 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF IFB: >=60 msec | 1 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Maximum QTCF Interval IFB: <30 msec | 8 participants |
Other Pre-specified
Number of Participants With Abnormal Fundoscopy Examination Findings
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)
Population: Safety analysis population included all enrolled participants who received at least 1 dose of Crizotinib on Cycle 1, Day 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Fundus: Mild Abnormality | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Optic Disc Notching: Mild Abnormality | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Optic Disc Notching: Mild Abnormality | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Retina Macula: Mild Abnormality | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Fundus: Mild Abnormality | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Vitreous Body: Mild Abnormality | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Retina Non-Macula: Mild Abnormality | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Retina Macula: Mild Abnormality | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Retina Non-Macula: Mild Abnormality | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Vitreous Body: Mild Abnormality | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Retina Non-Macula: Mild Abnormality | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Retina Macula: Mild Abnormality | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Optic Disc Notching: Mild Abnormality | 1 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Fundus: Mild Abnormality | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Vitreous Body: Mild Abnormality | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Retina Non-Macula: Mild Abnormality | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Vitreous Body: Mild Abnormality | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Fundus: Mild Abnormality | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Retina Macula: Mild Abnormality | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Optic Disc Notching: Mild Abnormality | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Fundus: Mild Abnormality | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Fundus: Mild Abnormality | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Retina Macula: Mild Abnormality | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Vitreous Body: Mild Abnormality | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Optic Disc Notching: Mild Abnormality | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Retina Non-Macula: Mild Abnormality | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Retina Non-Macula: Mild Abnormality | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Retina Macula: Mild Abnormality | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Optic Disc Notching: Mild Abnormality | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Vitreous Body: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Vitreous Body: Mild Abnormality | 1 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Fundus: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Retina Non-Macula: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Optic Disc Notching: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Retina Macula: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Retina Macula: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Retina Non-Macula: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Vitreous Body: Mild Abnormality | 1 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Fundus: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Optic Disc Notching: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Vitreous Body: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Fundus: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Vitreous Body: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Retina Non-Macula: Mild Abnormality | 1 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Retina Macula: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Fundus: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Optic Disc Notching: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Retina Macula: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Optic Disc Notching: Mild Abnormality | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Retina Non-Macula: Mild Abnormality | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Retina Non-Macula: Mild Abnormality | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Optic Disc Notching: Mild Abnormality | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Retina Non-Macula: Mild Abnormality | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Optic Disc Notching: Mild Abnormality | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Vitreous Body: Mild Abnormality | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Vitreous Body: Mild Abnormality | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Fundus: Mild Abnormality | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Fundus: Mild Abnormality | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Right Eye, Retina Macula: Mild Abnormality | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Abnormal Fundoscopy Examination Findings | Left Eye, Retina Macula: Mild Abnormality | 0 participants |
Other Pre-specified
Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities
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.
Time frame: Baseline up to end of treatment (up to 728 days)
Population: Safety analysis population included all enrolled participants who received at least 1 dose of Crizotinib on Cycle 1, Day 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 3 | 2 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypocalcemia: Grade 2 | 3 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST:Grade 1 | 6 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 1 | 5 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyponatremia: Grade 1 | 5 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | CR: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase(AP): Grade 1 | 4 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 2 | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 4 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 2 | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alanine aminotransferase (ALT): Grade 1 | 8 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 2 | 5 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypomagnesemia: Grade 1 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Creatinine (CR): Grade 1 | 9 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypokalemia: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 1 | 5 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase: Grade 2 | 2 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypermagnesemia: Grade 1 | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 4 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 2 | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | ALT: Grade 2 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 1 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | CR: Grade 2 | 2 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 1 | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypokalemia: Grade 1 | 4 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | ALT: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 2 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 1 | 2 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 2 | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyponatremia: Grade 3 | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypocalcemia: Grade 1 | 5 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoglycemia: Grade 1 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 2 | 2 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 1 | 8 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 4 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 1 | 3 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | CR: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | CR: Grade 2 | 4 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Creatinine (CR): Grade 1 | 11 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | ALT: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyponatremia: Grade 1 | 5 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypomagnesemia: Grade 1 | 2 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase(AP): Grade 1 | 7 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypokalemia: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase: Grade 2 | 1 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alanine aminotransferase (ALT): Grade 1 | 3 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypokalemia: Grade 1 | 1 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoglycemia: Grade 1 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase: Grade 3 | 1 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypocalcemia: Grade 2 | 1 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST:Grade 1 | 7 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 2 | 2 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypocalcemia: Grade 1 | 11 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 2 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 2 | 10 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 1 | 4 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 3 | 1 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyponatremia: Grade 3 | 4 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypermagnesemia: Grade 1 | 1 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 4 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 2 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 1 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | ALT: Grade 2 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 1 | 1 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 2 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 3 | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypocalcemia: Grade 2 | 9 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alanine aminotransferase (ALT): Grade 1 | 12 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | ALT: Grade 2 | 5 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | ALT: Grade 3 | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase(AP): Grade 1 | 8 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase: Grade 2 | 5 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase: Grade 3 | 3 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST:Grade 1 | 8 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 2 | 7 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 3 | 3 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 4 | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 1 | 2 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 2 | 3 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 3 | 2 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 4 | 2 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Creatinine (CR): Grade 1 | 8 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | CR: Grade 2 | 7 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | CR: Grade 3 | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 1 | 10 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 2 | 5 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 3 | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 1 | 4 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 2 | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 3 | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypermagnesemia: Grade 1 | 4 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 1 | 2 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 2 | 9 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 3 | 3 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypocalcemia: Grade 1 | 5 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoglycemia: Grade 1 | 2 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypokalemia: Grade 1 | 5 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypokalemia: Grade 3 | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypomagnesemia: Grade 1 | 5 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyponatremia: Grade 1 | 4 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 1 | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 2 | 3 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 3 | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyponatremia: Grade 3 | 7 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Creatinine (CR): Grade 1 | 6 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase(AP): Grade 1 | 4 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 3 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 3 | 1 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypomagnesemia: Grade 1 | 3 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | ALT: Grade 3 | 1 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyponatremia: Grade 1 | 5 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alanine aminotransferase (ALT): Grade 1 | 6 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypermagnesemia: Grade 1 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | CR: Grade 2 | 3 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 4 | 3 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | ALT: Grade 2 | 2 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | CR: Grade 3 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 2 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 3 | 5 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 1 | 8 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 3 | 5 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 1 | 1 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 2 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 2 | 3 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 2 | 8 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 1 | 2 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST:Grade 1 | 5 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 1 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypocalcemia: Grade 1 | 3 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 2 | 1 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 3 | 1 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypocalcemia: Grade 2 | 4 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 1 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase: Grade 3 | 3 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 2 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoglycemia: Grade 1 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase: Grade 2 | 3 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 3 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypokalemia: Grade 1 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 4 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyponatremia: Grade 3 | 5 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypokalemia: Grade 3 | 1 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 1 | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alanine aminotransferase (ALT): Grade 1 | 12 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 1 | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 2 | 7 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase: Grade 3 | 4 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 4 | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypomagnesemia: Grade 1 | 4 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 3 | 1 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | ALT: Grade 3 | 1 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoglycemia: Grade 1 | 2 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 3 | 3 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 2 | 14 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 3 | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 2 | 4 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | ALT: Grade 2 | 3 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyponatremia: Grade 1 | 7 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Creatinine (CR): Grade 1 | 6 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 3 | 5 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypokalemia: Grade 3 | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypocalcemia: Grade 2 | 9 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 1 | 3 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST:Grade 1 | 4 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | CR: Grade 2 | 8 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypermagnesemia: Grade 1 | 2 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 4 | 1 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 2 | 3 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 3 | 2 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 2 | 7 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | CR: Grade 3 | 1 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 2 | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase: Grade 2 | 4 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 3 | 8 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 1 | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase(AP): Grade 1 | 7 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 1 | 5 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyponatremia: Grade 3 | 7 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypocalcemia: Grade 1 | 4 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypokalemia: Grade 1 | 5 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 2 | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 2 | 2 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 3 | 4 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 1 | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 1 | 1 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 4 | 2 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 1 | 1 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 2 | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperkalemia: Grade 3 | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 3 | 7 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypermagnesemia: Grade 1 | 3 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST: Grade 2 | 3 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 1 | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 2 | 8 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | AST:Grade 1 | 4 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoalbuminemia: Grade 3 | 7 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 2 | 3 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase: Grade 3 | 6 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypocalcemia: Grade 2 | 9 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase: Grade 2 | 4 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypoglycemia: Grade 1 | 2 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypocalcemia: Grade 1 | 7 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypokalemia: Grade 1 | 4 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alkaline phosphatase(AP): Grade 1 | 5 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypokalemia: Grade 3 | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | ALT: Grade 3 | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypomagnesemia: Grade 1 | 6 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyponatremia: Grade 3 | 7 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | ALT: Grade 2 | 5 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Creatinine (CR): Grade 1 | 10 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 4 | 6 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyponatremia: Grade 1 | 8 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | CR: Grade 2 | 5 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | CR: Grade 3 | 1 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Bilirubin (total): Grade 3 | 10 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Alanine aminotransferase (ALT): Grade 1 | 9 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hyperglycemia: Grade 1 | 8 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Chemistry Test Abnormalities | Hypophosphatemia: Grade 3 | 1 participants |
Other Pre-specified
Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities
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.
Time frame: Baseline up to end of treatment (up to 728 days)
Population: Safety analysis population included all enrolled participants who received at least 1 dose of Crizotinib on Cycle 1, Day 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 2 | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Hemoglobin Increased: Grade 1 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 1 | 4 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 2 | 4 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 2 | 3 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 2 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 1 | 2 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 1 | 2 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 2 | 3 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 4 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 3 | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 1 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 3 | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 1 | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 2 | 7 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 1 | 2 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 2 | 1 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 3 | 1 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 1 | 7 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 2 | 1 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Hemoglobin Increased: Grade 1 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 1 | 3 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 1 | 2 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 3 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 3 | 1 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 2 | 7 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 2 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 4 | 0 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 1 | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 2 | 4 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Hemoglobin Increased: Grade 1 | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 3 | 3 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 3 | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 3 | 3 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 1 | 4 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 2 | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 2 | 2 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 2 | 3 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 1 | 1 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 4 | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 1 | 5 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 3 | 2 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 1 | 4 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 1 | 9 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 2 | 4 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 3 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 3 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 1 | 9 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 2 | 1 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 3 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Hemoglobin Increased: Grade 1 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 1 | 2 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 2 | 6 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 3 | 2 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 4 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 1 | 2 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 2 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 1 | 2 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 2 | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 3 | 3 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 1 | 2 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 2 | 2 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 3 | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 2 | 2 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Hemoglobin Increased: Grade 1 | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 4 | 2 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 1 | 2 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 1 | 8 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 2 | 9 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 3 | 1 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 3 | 2 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 3 | 1 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 2 | 3 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 1 | 7 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 3 | 2 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 2 | 3 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 3 | 1 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 2 | 5 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 1 | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 1 | 1 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Hemoglobin Increased: Grade 1 | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 1 | 3 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 3 | 4 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 1 | 8 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 2 | 2 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 2 | 7 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 1 | 1 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Platelets: Grade 3 | 5 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Lymphopenia: Grade 4 | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 3 | 3 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 1 | 1 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 3 | 1 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Anemia: Grade 2 | 5 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | White Blood Cells: Grade 2 | 3 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 2 | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 3 | 3 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Laboratory Test Abnormalities: NCI CTCAE (Version 4.0) Grade 1 to 4 Hematological Test Abnormalities | Neutrophils (Absolute): Grade 1 | 2 participants |
Other Pre-specified
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
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)
Population: Safety analysis population included all enrolled participants who received at least 1 dose of Crizotinib on Cycle 1, Day 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 11 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 7 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 15 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 8 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 20 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 13 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 9 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 6 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 16 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 14 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs | 16 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs | 14 participants |
Other Pre-specified
Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade
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)
Population: Safety analysis population included all enrolled participants who received at least 1 dose of Crizotinib on Cycle 1, Day 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 1 AEs | 1 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 4 AEs | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 2 AEs | 2 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 5 AEs | 2 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 3 AEs | 6 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 1 AEs | 2 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 5 AEs | 3 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 3 AEs | 3 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 4 AEs | 1 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 2 AEs | 6 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 4 AEs | 2 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 5 AEs | 6 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 3 AEs | 5 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 2 AEs | 5 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 1 AEs | 2 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 3 AEs | 2 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 1 AEs | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 2 AEs | 1 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 4 AEs | 1 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 5 AEs | 5 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 4 AEs | 2 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 1 AEs | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 5 AEs | 5 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 2 AEs | 0 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 3 AEs | 9 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 1 AEs | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 4 AEs | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 2 AEs | 1 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 5 AEs | 7 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Emergent Adverse Events, by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 4.0) Grade | Grade 3 AEs | 8 participants |
Other Pre-specified
Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
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)
Population: Safety analysis population included all enrolled participants who received at least 1 dose of Crizotinib on Cycle 1, Day 1.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 0 participants |
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE | 9 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 3 participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE | 14 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 0 participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE | 15 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 0 participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE | 6 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE | 11 participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 0 participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE | 11 participants |
Other Pre-specified
Objective Response Rate (ORR)
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)
Population: Response-evaluable population was defined as all participants in the safety analysis population who had an adequate baseline tumor assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Objective Response Rate (ORR) | 9.1 percentage of participants |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Objective Response Rate (ORR) | 0 percentage of participants |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Objective Response Rate (ORR) | 5.0 percentage of participants |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Objective Response Rate (ORR) | 0 percentage of participants |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Objective Response Rate (ORR) | 6.3 percentage of participants |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Objective Response Rate (ORR) | 0 percentage of participants |
Other Pre-specified
Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: 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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: Cycle 2 Day 1 | 257.7 ng*hr/mL | Geometric Coefficient of Variation 38 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: Cycle 2 Day 1 | 166.1 ng*hr/mL | Geometric Coefficient of Variation 73 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: Cycle 2 Day 1 | 279.4 ng*hr/mL | Geometric Coefficient of Variation 95 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: Cycle 2 Day 1 | 124.6 ng*hr/mL | Geometric Coefficient of Variation 85 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: Cycle 2 Day 1 | 337.0 ng*hr/mL | Geometric Coefficient of Variation 59 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of Crizotinib: Cycle 2 Day 1 | 161.9 ng*hr/mL | Geometric Coefficient of Variation 48 |
Comparison: CI: Geometric mean ratio and 90% CI were derived from ANOVA model.90% CI: [63.47, 185.26]
Comparison: CI: Geometric mean ratio and 90% CI were derived from ANOVA model.90% CI: [120.96, 340.3]
Comparison: CI: Geometric mean ratio and 90% CI were derived from ANOVA model.90% CI: [86.61, 197.47]
Comparison: CI: Geometric mean ratio and 90% CI were derived from ANOVA model.90% CI: [42.54, 92.78]
Other Pre-specified
Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1
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
Population: 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 | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Hepatic Function: Crizotinib 250 mg Twice Daily | Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1 | 82.56 ng*hr/mL | Geometric Coefficient of Variation 36 |
| Normal Hepatic Function: Crizotinib 200/250 mg Twice Daily | Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1 | 54.85 ng*hr/mL | Geometric Coefficient of Variation 99 |
| Mild Hepatic Impairment: Crizotinib 250 mg Twice Daily | Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1 | 46.66 ng*hr/mL | Geometric Coefficient of Variation 181 |
| Moderate Hepatic Impairment: Crizotinib 250 mg Once Daily | Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1 | 11.56 ng*hr/mL | Geometric Coefficient of Variation 49 |
| Moderate Hepatic Impairment Crizotinib 200 mg Twice Daily | Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1 | 39.41 ng*hr/mL | Geometric Coefficient of Variation 119 |
| Severe Hepatic Impairment Crizotinib 250 mg Once Daily | Unbound Area Under the Plasma Concentration Time Curve as Daily Exposure (AUCdaily) of PF-06260182: Cycle 2 Day 1 | 22.49 ng*hr/mL | Geometric Coefficient of Variation 79 |