Healthy
Conditions
Keywords
crizotinib, healthy volunteers, ketoconazole, pharmacokinetics, single dose
Brief summary
The purpose of this study is to estimate the effect of multiple doses of ketoconazole on the single dose pharmacokinetics of crizotinib in healthy volunteers.
Interventions
DRUGcrizotinib
Treatment A: a single 150-mg dose of crizotinib will be administered in the fasted state on Day 1 as 1 × 50-mg and 1 × 100-mg Immediate Release Tablets.
DRUGketoconazole
Treatment B: 200 mg twice a day (approximately 12 hrs apart) doses of ketoconazole will be administered orally on an empty stomach from Day 1 to Day 16.
Sponsors
Pfizer
Study design
Allocation
NON_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-child bearing 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 with evidence of disease, conditions affecting drug absorption, treatment with other investigational drug within 30 days, history of regular alcohol consumption, and use of prescription , nonprescription drugs and dietary supplement within 7 days, and 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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 | 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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 | — |
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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 | 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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 | 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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 | 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) 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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 | Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast) of crizotinib metabolite (PF-06260182). |
| 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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 | 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-∞) of crizotinib metabolite (PF-06260182). |
| 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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 | Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast). |
| 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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 | — |
| Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Last Quantifiable Concentration for Crizotinib Metabolite Ratio (MRAUClast) | 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 | Molar ratio of metabolite to parent area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (MRAUClast). |
| Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Extrapolated Infinite Time [MRAUC(0-∞)] | 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 | Molar ratio of metabolite to parent area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞) \[MRAUC(0-∞)\]. |
| Metabolite to Parent Ratio of Maximum Observed Plasma Concentration (MRCmax) | 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 | Metabolite to parent molar ratio of maximum observed plasma concentration (Cmax). |
| 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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 | — |
| 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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes participants randomized to receive Crizotinib 150 mg IRT first and then Crizotinib 150 mg + Ketoconazole 200 mg BID | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 36.5 years STANDARD_DEVIATION 7.6 |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 15 | 4 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2
Population: The pharmacokinetic (PK) parameter analysis population included all participants enrolled and treated 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 150 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | 1260.00 ng*hr/mL | Standard Deviation 318.04 |
| Crizotinib 150 mg + Ketoconazole 200 mg BID | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] | 3986.00 ng*hr/mL | Standard Deviation 1010.1 |
Comparison: Natural log transformed AUC (0-∞) of crizotinib was analyzed using a mixed effect model with treatment as fixed effect and subject as a random effect. The adjusted mean differences and 90% confidence intervals (CIs) for the differences was exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [286.17, 349.73]
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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all participants enrolled and treated 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 150 mg | Maximum Observed Plasma Concentration (Cmax) | 65.540 ng/mL | Standard Deviation 24.486 |
| Crizotinib 150 mg + Ketoconazole 200 mg BID | Maximum Observed Plasma Concentration (Cmax) | 94.470 ng/mL | Standard Deviation 19.082 |
Comparison: Natural log transformed Cmax of crizotinib was analyzed using a mixed effect model with treatment as fixed effect and subject as a random effect. The adjusted mean differences and 90% CIs for the differences was exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [126.42, 164.33]
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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all participants enrolled and treated 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 150 mg | Apparent Oral Clearance (CL/F) | 122.600 L/hr | Standard Deviation 31.382 |
| Crizotinib 150 mg + Ketoconazole 200 mg BID | Apparent Oral Clearance (CL/F) | 38.850 L/hr | Standard Deviation 10.413 |
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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all participants enrolled and treated 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 150 mg | Apparent Volume of Distribution (Vz/F) | 6580.0 L | Standard Deviation 1881.8 |
| Crizotinib 150 mg + Ketoconazole 200 mg BID | Apparent Volume of Distribution (Vz/F) | 3122.0 L | Standard Deviation 1131.2 |
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-∞) 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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all participants enrolled and treated 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 150 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Crizotinib Metabolite (PF-06260182) | 178.100 ng*hr/mL | Standard Deviation 57.989 |
| Crizotinib 150 mg + Ketoconazole 200 mg BID | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Crizotinib Metabolite (PF-06260182) | 920.600 ng*hr/mL | Standard Deviation 343.42 |
Comparison: Natural log transformed AUC (0-∞) of crizotinib metabolite (PF-06260182) was analyzed using a mixed effect model with treatment as fixed effect and subject as a random effect. The adjusted mean differences and 90% CIs for the differences was exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [457.88, 583.72]
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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all participants enrolled and treated 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 150 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 1197.00 ng*hr/mL | Standard Deviation 308.18 |
| Crizotinib 150 mg + Ketoconazole 200 mg BID | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 3929.00 ng*hr/mL | Standard Deviation 1004.4 |
Comparison: Natural log transformed AUClast of crizotinib was analyzed using a mixed effect model with treatment as fixed effect and subject as a random effect. The adjusted mean differences and 90% CIs for the differences was exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [296.42, 363.63]
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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all participants enrolled and treated 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 150 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) | 172.700 ng*hr/mL | Standard Deviation 56.751 |
| Crizotinib 150 mg + Ketoconazole 200 mg BID | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) | 897.400 ng*hr/mL | Standard Deviation 337.92 |
Comparison: Natural log transformed AUClast of crizotinib metabolite (PF-06260182) was analyzed using a mixed effect model with treatment as fixed effect and subject as a random effect. The adjusted mean differences and 90% CIs for the differences was exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [460.42, 586.5]
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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all participants enrolled and treated 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 150 mg | Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) | 16.6900 ng/mL | Standard Deviation 4.8538 |
| Crizotinib 150 mg + Ketoconazole 200 mg BID | Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) | 26.9400 ng/mL | Standard Deviation 5.4113 |
Comparison: Natural log transformed Cmax of crizotinib was analyzed using a mixed effect model with treatment as fixed effect and subject as a random effect. The adjusted mean differences and 90% CIs for the differences was exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [143.09, 182.09]
Secondary
Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Extrapolated Infinite Time [MRAUC(0-∞)]
Molar ratio of metabolite to parent area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞) \[MRAUC(0-∞)\].
Time frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all participants enrolled and treated 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 150 mg | Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Extrapolated Infinite Time [MRAUC(0-∞)] | 0.1371 Ratio | Standard Deviation 0.0188 |
| Crizotinib 150 mg + Ketoconazole 200 mg BID | Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Extrapolated Infinite Time [MRAUC(0-∞)] | 0.2239 Ratio | Standard Deviation 0.0398 |
Secondary
Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Last Quantifiable Concentration for Crizotinib Metabolite Ratio (MRAUClast)
Molar ratio of metabolite to parent area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (MRAUClast).
Time frame: 0 (Pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all participants enrolled and treated 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 150 mg | Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Last Quantifiable Concentration for Crizotinib Metabolite Ratio (MRAUClast) | 0.1399 Ratio | Standard Deviation 0.0194 |
| Crizotinib 150 mg + Ketoconazole 200 mg BID | Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Last Quantifiable Concentration for Crizotinib Metabolite Ratio (MRAUClast) | 0.2217 Ratio | Standard Deviation 0.0397 |
Secondary
Metabolite to Parent Ratio of Maximum Observed Plasma Concentration (MRCmax)
Metabolite to parent molar ratio of 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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all participants enrolled and treated 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 150 mg | Metabolite to Parent Ratio of Maximum Observed Plasma Concentration (MRCmax) | 0.2469 Ratio | Standard Deviation 0.0634 |
| Crizotinib 150 mg + Ketoconazole 200 mg BID | Metabolite to Parent Ratio of Maximum Observed Plasma Concentration (MRCmax) | 0.2766 Ratio | Standard Deviation 0.0511 |
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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crizotinib 150 mg | Plasma Decay Half-Life (t1/2) | 37.1300 hr | Standard Deviation 4.3606 |
| Crizotinib 150 mg + Ketoconazole 200 mg BID | Plasma Decay Half-Life (t1/2) | 54.8700 hr | Standard Deviation 6.2589 |
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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Crizotinib 150 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 5.0 hr |
| Crizotinib 150 mg + Ketoconazole 200 mg BID | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 6.0 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 in period 1 and day 0, 0 (pre-dose), 1, 2, 4, 6, 8, 10, 12, 24, 48, 72, 96, 144, 192 and 312 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all participants enrolled and treated who had at least 1 of the PK parameters of primary interest in at least 1 treatment period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Crizotinib 150 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182) | 5.0 hr |
| Crizotinib 150 mg + Ketoconazole 200 mg BID | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182) | 8.0 hr |