Healthy
Conditions
Keywords
crizotinib, healthy volunteers, rifampin, pharmacokinetics, single dose
Brief summary
The purpose of this study is to estimate the effect of multiple doses of Rifampin on the single dose pharmacokinetics of Crizotinib in healthy volunteers.
Interventions
DRUGcrizotinib
Treatment A: a single 250-mg dose of crizotinib will be administered in the fasted state on Day 1 as 1 × 50-mg and 2 × 100-mg Immediate Release Tablets.
DRUGrifampin
Treatment B: 600 mg once a day doses of rifampin will be orally administered after overnight fasting from Day 1 to Day 14.
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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 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 CL/F 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 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 - ∞) of crizotinib metabolite (PF-06260182). It is obtained from AUC (0 - t) plus AUC (t - ∞). |
| 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2 | — |
| Metabolite to Parent Ratio Area Under the Curve From Time Zero to Last Quantifiable Concentration (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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 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 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2 | Molar ratio of metabolite to parent area under the curve from time zero to extrapolated infinite time \[MRAUC (0-∞)\]. |
| Metabolite to Parent Ratio 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2 | Metabolite to parent molar ratio of maximum observed plasma concentration (MRCmax). |
| 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 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 250 mg IRT first and then crizotinib 250 mg + rifampin 600 mg. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention Period | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 38.9 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 15 | 3 / 14 |
| serious Total, serious adverse events | 0 / 15 | 0 / 14 |
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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
Population: The pharmacokinetic (PK) parameter analysis population included all enrolled 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 250 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 2192.00 ng*hr/mL | Standard Deviation 616.59 |
| Crizotinib 250 mg + Rifampin 600 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] | 397.20 ng*hr/mL | Standard Deviation 106.12 |
Comparison: Natural log transformed AUC (0-∞) of crizotinib was analyzed using a mixed effect model with treatment as a fixed effect and participant 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: [16.14, 20.54]
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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all enrolled 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 250 mg | Maximum Observed Plasma Concentration (Cmax) | 102.10 ng/mL | Standard Deviation 35.64 |
| Crizotinib 250 mg + Rifampin 600 mg | Maximum Observed Plasma Concentration (Cmax) | 32.06 ng/mL | Standard Deviation 11.23 |
Comparison: Natural log transformed Cmax of crizotinib was analyzed using a mixed effect model with treatment as a fixed effect and participant 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: [26.43, 37.51]
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 CL/F 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all enrolled 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 250 mg | Apparent Oral Clearance (CL/F) | 118.80 L/hr | Standard Deviation 37.39 |
| Crizotinib 250 mg + Rifampin 600 mg | Apparent Oral Clearance (CL/F) | 648.60 L/hr | Standard Deviation 164.95 |
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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all enrolled 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 250 mg | Apparent Volume of Distribution (Vz/F) | 5940.0 L | Standard Deviation 3242.9 |
| Crizotinib 250 mg + Rifampin 600 mg | Apparent Volume of Distribution (Vz/F) | 45720.0 L | Standard Deviation 15766 |
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 - ∞) of crizotinib metabolite (PF-06260182). 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 in period 1 and Day 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 2
Population: The PK parameter analysis population included all enrolled 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 250 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for Crizotinib Metabolite (PF-06260182) | 378.60 ng*hr/mL | Standard Deviation 120.38 |
| Crizotinib 250 mg + Rifampin 600 mg | Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] for Crizotinib Metabolite (PF-06260182) | 21.78 ng*hr/mL | Standard Deviation 8.98 |
Comparison: Natural log transformed AUC (0 - ∞) of PF-06260182 was analyzed using a mixed effect model with treatment as a fixed effect and participant 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: [4.86, 6.81]
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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all enrolled 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 250 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 2103.00 ng*hr/mL | Standard Deviation 620.52 |
| Crizotinib 250 mg + Rifampin 600 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 368.60 ng*hr/mL | Standard Deviation 101.93 |
Comparison: Natural log transformed AUClast of crizotinib was analyzed using a mixed effect model with treatment as a fixed effect and participant 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: [15.48, 20.02]
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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all enrolled 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 250 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) | 369.50 ng*hr/mL | Standard Deviation 119.58 |
| Crizotinib 250 mg + Rifampin 600 mg | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) | 20.28 ng*hr/mL | Standard Deviation 8.19 |
Comparison: Natural log transformed AUClast of PF-06260182 was analyzed using a mixed effect model with treatment as a fixed effect and participant 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: [4.64, 6.49]
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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all enrolled 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 250 mg | Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) | 29.88 ng/mL | Standard Deviation 10.22 |
| Crizotinib 250 mg + Rifampin 600 mg | Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) | 3.29 ng/mL | Standard Deviation 1.23 |
Comparison: Natural log transformed Cmax of PF-06260182 was analyzed using a mixed effect model with treatment as a fixed effect and participant 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: [9.02, 13.45]
Secondary
Metabolite to Parent Ratio Area Under the Curve From Time Zero to Extrapolated Infinite Time [MRAUC (0 - ∞)]
Molar ratio of metabolite to parent area under the curve from time zero to extrapolated infinite time \[MRAUC (0-∞)\].
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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all enrolled 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 250 mg | Metabolite to Parent Ratio Area Under the Curve From Time Zero to Extrapolated Infinite Time [MRAUC (0 - ∞)] | 0.1676 Ratio | Standard Deviation 0.0271 |
| Crizotinib 250 mg + Rifampin 600 mg | Metabolite to Parent Ratio Area Under the Curve From Time Zero to Extrapolated Infinite Time [MRAUC (0 - ∞)] | 0.0532 Ratio | Standard Deviation 0.0113 |
Secondary
Metabolite to Parent Ratio Area Under the Curve From Time Zero to Last Quantifiable Concentration (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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all enrolled 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 250 mg | Metabolite to Parent Ratio Area Under the Curve From Time Zero to Last Quantifiable Concentration (MRAUClast) | 0.1703 Ratio | Standard Deviation 0.0264 |
| Crizotinib 250 mg + Rifampin 600 mg | Metabolite to Parent Ratio Area Under the Curve From Time Zero to Last Quantifiable Concentration (MRAUClast) | 0.0533 Ratio | Standard Deviation 0.0112 |
Secondary
Metabolite to Parent Ratio Maximum Observed Plasma Concentration (MRCmax)
Metabolite to parent molar ratio of maximum observed plasma concentration (MRCmax).
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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all enrolled 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 250 mg | Metabolite to Parent Ratio Maximum Observed Plasma Concentration (MRCmax) | 0.2839 Ratio | Standard Deviation 0.0711 |
| Crizotinib 250 mg + Rifampin 600 mg | Metabolite to Parent Ratio Maximum Observed Plasma Concentration (MRCmax) | 0.0996 Ratio | Standard Deviation 0.0382 |
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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all enrolled 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 250 mg | Plasma Decay Half-Life (t1/2) | 33.07 hr | Standard Deviation 6.96 |
| Crizotinib 250 mg + Rifampin 600 mg | Plasma Decay Half-Life (t1/2) | 48.23 hr | Standard Deviation 5.62 |
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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 hrs post crizotinib dose in period 2
Population: The PK parameter analysis population included all enrolled 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 250 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 5.0 hr |
| Crizotinib 250 mg + Rifampin 600 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 3.0 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, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96 and 144 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 250 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182) | 5.0 hr |
| Crizotinib 250 mg + Rifampin 600 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182) | 5.0 hr |