Healthy
Conditions
Keywords
bioequivalence, food effect, pharmacokinetics, crizotinib
Brief summary
The purpose of this study is to demonstrate bioequivalence of the Commercial Image Capsule (CIC) relative to the Immediate Release Tablet (IRT) of crizotinib, bioequivalence of CIC relative to Powder in Capsule (PIC) of crizotinib, and lack of an effect of high fat meal on the pharmacokinetics (PK) of crizotinib when administered as CIC Formulation in healthy volunteers.
Detailed description
The purpose of this study is to demonstrate bioequivalence of the CIC relative to IRT and CIC relative to PIC, and lack of an effect of food on the PK of crizotinib in healthy volunteers.
Interventions
DRUGcrizotinib
Treatment A (Reference 1): a 250 mg single dose of crizotinib administered in a fasted state as 1 × 50-mg IRT and 2 × 100-mg IRTs. Treatment B (Reference 2): a 250 mg single dose of crizotinib administered in a fasted state as 1 × 50-mg PIC and 2 × 100 mg PICs. Treatment C (Test for BE, Reference for Food Effect): a 250 mg single dose of crizotinib administered in a fasted state as 1 × 250-mg CIC. Treatment D (Test High Fat): a 250 mg single dose of crizotinib administered with a high-fat meal as 1 × 250-mg CIC
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and/or female of non-childbearing potential subjects between the ages of 18 and 55 years, inclusive (Healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead ECG and clinical laboratory tests). * Body Mass Index (BMI) of 17.5 to 30.5 kg/m\^2; and a total body weight \>50 kg (110 lbs)
Exclusion criteria
* Subjects who are smoking, or with evidence of disease, conditions affecting absorption, treatment with other investigational drug within 30 days, history of regular alcohol consumption, use of prescription, nonprescription drugs and dietary supplement within 7 days, or blood donation of 500 mL within 56 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hours (hrs) post crizotinib dose | AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞). |
| Maximum Observed Plasma Concentration (Cmax) | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Decay Half Life (t1/2) | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Apparent Oral Clearance (CL/F) | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose | Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. |
| Apparent Volume of Distribution (Vz/F) | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose | Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast). |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) for Crizotinib Metabolite (PF-06260182) | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose | AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞). |
| Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182) | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose | — |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose | Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast) of Crizotinib metabolite (PF-06260182). |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose | — |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes participants randomized to receive any treatment (crizotinib 250 mg IRT fasted first, crizotinib 250 mg PIC fasted first, crizotinib 250 mg CIC fasted first and crizotinib 250 mg CIC fed). | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Fourth Intervention Period | Withdrawal by Subject | 1 | 0 | 0 | 0 |
| Third Intervention Period | Adverse Event | 0 | 1 | 0 | 0 |
| Washout Period (at Least 14 Days) | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 38.9 years STANDARD_DEVIATION 8.1 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 21 / 36 | 24 / 36 | 20 / 36 | 21 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 | 0 / 36 | 0 / 36 |
Outcome results
Primary
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞])
AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞).
Time frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hours (hrs) post crizotinib dose
Population: Pharmacokinetic (PK) parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Crizotinib IRT Fasted | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) | 2890.0 ng*hr/mL | Standard Deviation 1021.8 |
| Crizotinib PIC Fasted | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) | 2665.0 ng*hr/mL | Standard Deviation 1190.4 |
| Crizotinib CIC Fasted | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) | 2887.0 ng*hr/mL | Standard Deviation 1109.6 |
| Crizotinib CIC Fed | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) | 2475.0 ng*hr/mL | Standard Deviation 1037.7 |
Comparison: Natural log transformed AUC (0-∞) of crizotinib was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% confidence intervals (CIs) for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [91.49, 108.33]
Comparison: Natural log transformed AUC (0-∞) of crizotinib was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [98.26, 116.35]
Comparison: Natural log transformed AUC (0-∞) of crizotinib was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [78.88, 93.25]
Primary
Maximum Observed Plasma Concentration (Cmax)
Time frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Crizotinib IRT Fasted | Maximum Observed Plasma Concentration (Cmax) | 126.00 ng/mL | Standard Deviation 36.58 |
| Crizotinib PIC Fasted | Maximum Observed Plasma Concentration (Cmax) | 119.30 ng/mL | Standard Deviation 50.88 |
| Crizotinib CIC Fasted | Maximum Observed Plasma Concentration (Cmax) | 135.00 ng/mL | Standard Deviation 47.84 |
| Crizotinib CIC Fed | Maximum Observed Plasma Concentration (Cmax) | 116.10 ng/mL | Standard Deviation 45.58 |
Comparison: Natural log transformed Cmax of crizotinib was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [96.55, 118.51]
Comparison: Natural log transformed Cmax of crizotinib was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [100.47, 123.33]
Comparison: Natural log transformed Cmax of crizotinib was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [77.89, 95.43]
Secondary
Apparent Oral Clearance (CL/F)
Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Time frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Crizotinib IRT Fasted | Apparent Oral Clearance (CL/F) | 86.49 L/hr | Standard Deviation 30.42 |
| Crizotinib PIC Fasted | Apparent Oral Clearance (CL/F) | 93.78 L/hr | Standard Deviation 49.8 |
| Crizotinib CIC Fasted | Apparent Oral Clearance (CL/F) | 86.57 L/hr | Standard Deviation 53.63 |
| Crizotinib CIC Fed | Apparent Oral Clearance (CL/F) | 101.00 L/hr | Standard Deviation 38.6 |
Secondary
Apparent Volume of Distribution (Vz/F)
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Time frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Crizotinib IRT Fasted | Apparent Volume of Distribution (Vz/F) | 4290.0 L | Standard Deviation 1672.4 |
| Crizotinib PIC Fasted | Apparent Volume of Distribution (Vz/F) | 4703.0 L | Standard Deviation 2874.7 |
| Crizotinib CIC Fasted | Apparent Volume of Distribution (Vz/F) | 4313.0 L | Standard Deviation 3880.9 |
| Crizotinib CIC Fed | Apparent Volume of Distribution (Vz/F) | 5096.0 L | Standard Deviation 2302 |
Secondary
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) for Crizotinib Metabolite (PF-06260182)
AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞).
Time frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period. Here, the 'N = 35' is signifying those participants who were evaluable for this measure at the specified time point for crizotinib CIC fed arm group.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Crizotinib IRT Fasted | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) for Crizotinib Metabolite (PF-06260182) | 442.00 ng*hr/mL | Standard Deviation 221.96 |
| Crizotinib PIC Fasted | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) for Crizotinib Metabolite (PF-06260182) | 402.10 ng*hr/mL | Standard Deviation 257.39 |
| Crizotinib CIC Fasted | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) for Crizotinib Metabolite (PF-06260182) | 447.10 ng*hr/mL | Standard Deviation 248.23 |
| Crizotinib CIC Fed | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) for Crizotinib Metabolite (PF-06260182) | 341.80 ng*hr/mL | Standard Deviation 194.91 |
Comparison: Natural log transformed AUC (0-∞) of PF-06260182 was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [90.46, 110.73]
Comparison: Natural log transformed AUC (0-∞) of PF-06260182 was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [98.03, 120.02]
Comparison: Natural log transformed AUC (0-∞) of PF-06260182 was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [69.23, 84.74]
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast).
Time frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Crizotinib IRT Fasted | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 2763.0 ng*hr/mL | Standard Deviation 989 |
| Crizotinib PIC Fasted | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 2531.0 ng*hr/mL | Standard Deviation 1158 |
| Crizotinib CIC Fasted | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 2761.0 ng*hr/mL | Standard Deviation 1078.4 |
| Crizotinib CIC Fed | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 2359.0 ng*hr/mL | Standard Deviation 1013 |
Comparison: Natural log transformed AUClast of crizotinib was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [91.3, 108.66]
Comparison: Natural log transformed AUClast of crizotinib was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [98.58, 117.35]
Comparison: Natural log transformed AUClast of crizotinib was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [78.45, 93.22]
Secondary
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182)
Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast) of Crizotinib metabolite (PF-06260182).
Time frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Crizotinib IRT Fasted | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) | 432.20 ng*hr/mL | Standard Deviation 219.76 |
| Crizotinib PIC Fasted | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) | 391.20 ng*hr/mL | Standard Deviation 255.12 |
| Crizotinib CIC Fasted | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) | 436.90 ng*hr/mL | Standard Deviation 246.34 |
| Crizotinib CIC Fed | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) | 325.00 ng*hr/mL | Standard Deviation 192.81 |
Comparison: Natural log transformed AUClast of PF-06260182 was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [90.16, 110.97]
Comparison: Natural log transformed AUClast of PF-06260182 was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [98.11, 120.77]
Comparison: Natural log transformed AUClast of PF-06260182 was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [67.55, 82.98]
Secondary
Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182)
Time frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Crizotinib IRT Fasted | Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) | 32.20 ng/mL | Standard Deviation 12.48 |
| Crizotinib PIC Fasted | Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) | 29.74 ng/mL | Standard Deviation 15.19 |
| Crizotinib CIC Fasted | Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) | 33.04 ng/mL | Standard Deviation 12.12 |
| Crizotinib CIC Fed | Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) | 23.64 ng/mL | Standard Deviation 10.85 |
Comparison: Natural log transformed Cmax of PF-06260182 was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [92.84, 112.31]
Comparison: Natural log transformed Cmax of PF-06260182 was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [98.98, 119.75]
Comparison: Natural log transformed Cmax of PF-06260182 was analyzed using a mixed effect model with sequence, period and treatment as fixed effects and participant within sequence as a random effect. The adjusted mean differences and 90% CIs for the differences were exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [65.46, 79.05]
Secondary
Plasma Decay Half Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crizotinib IRT Fasted | Plasma Decay Half Life (t1/2) | 34.62 hr | Standard Deviation 4.13 |
| Crizotinib PIC Fasted | Plasma Decay Half Life (t1/2) | 35.28 hr | Standard Deviation 6.39 |
| Crizotinib CIC Fasted | Plasma Decay Half Life (t1/2) | 34.85 hr | Standard Deviation 4.94 |
| Crizotinib CIC Fed | Plasma Decay Half Life (t1/2) | 35.41 hr | Standard Deviation 5.49 |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Crizotinib IRT Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 5.00 hr |
| Crizotinib PIC Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 5.00 hr |
| Crizotinib CIC Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 5.00 hr |
| Crizotinib CIC Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 5.00 hr |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182)
Time frame: 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose
Population: PK parameter analysis population included all randomized and treated participants who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Crizotinib IRT Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182) | 6.00 hr |
| Crizotinib PIC Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182) | 6.00 hr |
| Crizotinib CIC Fasted | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182) | 5.00 hr |
| Crizotinib CIC Fed | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182) | 6.00 hr |