Healthy
Conditions
Keywords
healthy volunteers, crizotinib, absolute bioavailability, pharmacokinetics
Brief summary
This study will be an open-label, randomized, 2-period, 2-treatment, 2-sequence, cross-over single-dose study to test the absolute bioavailability of oral crizotinib formulation to IV formulation in healthy adult volunteers. Fourteen (14) subjects will be enrolled to obtain at least 12 evaluable subjects who complete the study. Each subject will receive two treatments (A and B) with a washout period of at least 14 days between each treatment.
Detailed description
evaluate the absolute bioavailability of oral crizotinib to IV crizotinib.
Interventions
DRUGcrizotinib
Treatment A: Intravenous dose of 50 mg crizotinib will be administered as directed.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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
* Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). * Any condition possibly affecting drug absorption (eg, gastrectomy). * A positive urine drug screen. * History of regular alcohol consumption exceeding 14 drinks/week for females or 21 drinks/week for males within 6 months of screening. * Treatment with an investigational drug within 30 days (or as determined by the local requirement, whichever is longer) or 5 half-lives preceding the first dose of study medication. * 12-lead ECG demonstrating QTc \>450 msec at Screening. * Pregnant or nursing females; females of childbearing potential, including those with tubal ligation. * Use of prescription or nonprescription drugs and dietary supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication. Herbal supplements and hormone replacement therapy must be discontinued 28 days prior to the first dose of study medication. * Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. * A positive serology for Hepatitis B or Hepatitis C. * Subjects who are currently smoking.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞][dn]) | 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hours (hrs) post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B | AUC \[0 - ∞\]\[dn\] = Dose normalized area under the plasma concentration versus time curve (AUC\[dn\]) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - ∞) divided by dose. |
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) | 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B | 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 - ∞). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) | 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B | — |
| 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 oral crizotinib dose in Treatment B | — |
| Plasma Decay Half Life (t1/2) | 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B | 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 oral crizotinib dose in Treatment B | 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. |
| Systemic Clearance (CL) | 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A | CL is a quantitative measure of the rate at which a drug substance is removed from the body. |
| 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 oral crizotinib dose in Treatment B | 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 plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. |
| Volume of Distribution at Steady State (Vss) | 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A | 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. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B | 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 oral crizotinib dose in Treatment B | 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). |
| Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) | 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B | — |
| 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 oral crizotinib dose in Treatment B | — |
| 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, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B | 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 oral crizotinib dose in Treatment B | 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 Maximum Observed Plasma Concentration (MRCmax) | 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B | Metabolite to parent molar ratio of maximum observed plasma concentration (MRCmax). |
| Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) | 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B | Area under the plasma concentration time-curve from zero (pre-dose) to the last measured concentration (AUClast) of crizotinib metabolite (PF-06260182). |
| Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) | 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B | AUClast\[dn\] = Dose normalized area under the plasma concentration time-curve (AUC\[dn\]) from zero to the last measured concentration. |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes participants randomized to receive crizotinib 50 mg IV first and crizotinib 250 mg oral first. | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age Continuous | 35.7 years STANDARD_DEVIATION 11.5 |
| Sex: Female, Male Female | 0 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 | 8 / 14 | 5 / 14 |
| serious Total, serious adverse events | 0 / 14 | 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, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B
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 50 mg IV | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) | 1067.00 ng*hr/mL | Standard Deviation 198.54 |
| Crizotinib 250 mg Oral | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) | 2321.00 ng*hr/mL | Standard Deviation 833.14 |
Primary
Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞][dn])
AUC \[0 - ∞\]\[dn\] = Dose normalized area under the plasma concentration versus time curve (AUC\[dn\]) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - ∞) divided by dose.
Time frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hours (hrs) post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B
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 50 mg IV | Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞][dn]) | 21.36 ng*hr/mL/mg | Standard Deviation 3.99 |
| Crizotinib 250 mg Oral | Dose Normalized Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞][dn]) | 9.28 ng*hr/mL/mg | Standard Deviation 3.32 |
Comparison: Natural log transformed AUC (0 - ∞)(dn) of crizotinib was analyzed using 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 was exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [39.68, 47.56]
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 oral crizotinib dose in Treatment B
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 50 mg IV | Apparent Oral Clearance (CL/F) | 107.7 L/hr | Standard Deviation 36.1 |
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 plasma 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 oral crizotinib dose in Treatment B
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 50 mg IV | Apparent Volume of Distribution (Vz/F) | 4478.0 L | Standard Deviation 1665.3 |
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 oral crizotinib dose in Treatment B
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 = 13' is signifying those participants who were evaluable for this measure at the specified time point for this arm group.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Crizotinib 50 mg IV | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUC [0 - ∞]) for Crizotinib Metabolite (PF-06260182) | 360.4 ng*hr/mL | Standard Deviation 117.2 |
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, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B
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 50 mg IV | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 1007.00 ng*hr/mL | Standard Deviation 182.84 |
| Crizotinib 250 mg Oral | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) | 2250.00 ng*hr/mL | Standard Deviation 821.3 |
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, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B
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 50 mg IV | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) | 35.61 ng*hr/mL | Standard Deviation 17.64 |
| Crizotinib 250 mg Oral | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) for Crizotinib Metabolite (PF-06260182) | 342.70 ng*hr/mL | Standard Deviation 116.22 |
Secondary
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn])
AUClast\[dn\] = Dose normalized area under the plasma concentration time-curve (AUC\[dn\]) from zero to the last measured concentration.
Time frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B
Population: 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 50 mg IV | Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) | 20.14 ng*hr/mL/mg | Standard Deviation 3.63 |
| Crizotinib 250 mg Oral | Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast[dn]) | 9.00 ng*hr/mL/mg | Standard Deviation 3.28 |
Comparison: Natural log transformed AUClast(dn) of crizotinib was analyzed using 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 was exponentiated to provide estimates of the ratio of adjusted geometric means (Test/Reference) and 90% CIs for the ratios.90% CI: [40.9, 48.78]
Secondary
Maximum Observed Plasma Concentration (Cmax)
Time frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B
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 50 mg IV | Maximum Observed Plasma Concentration (Cmax) | 155.00 ng/mL | Standard Deviation 29.57 |
| Crizotinib 250 mg Oral | Maximum Observed Plasma Concentration (Cmax) | 99.60 ng/mL | Standard Deviation 28.82 |
Secondary
Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182)
Time frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B
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 50 mg IV | Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) | 3.01 ng/mL | Standard Deviation 1.46 |
| Crizotinib 250 mg Oral | Maximum Observed Plasma Concentration (Cmax) for Crizotinib Metabolite (PF-06260182) | 26.46 ng/mL | Standard Deviation 6.41 |
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 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 oral crizotinib dose in Treatment B
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 = 13' is signifying those participants who were evaluable for this measure at the specified time point for this arm group.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Crizotinib 50 mg IV | Metabolite to Parent Ratio Area Under the Curve From Time Zero to Extrapolated Infinite Time (MRAUC [0-∞]) | 0.144 Ratio | Standard Deviation 0.019 |
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, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B
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 50 mg IV | Metabolite to Parent Ratio Maximum Observed Plasma Concentration (MRCmax) | 0.019 Ratio | Standard Deviation 0.007 |
| Crizotinib 250 mg Oral | Metabolite to Parent Ratio Maximum Observed Plasma Concentration (MRCmax) | 0.258 Ratio | Standard Deviation 0.043 |
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, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B
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 50 mg IV | Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Last Quantifiable Concentration for Crizotinib Metabolite Ratio (MRAUClast) | 0.034 Ratio | Standard Deviation 0.011 |
| Crizotinib 250 mg Oral | Metabolite to Parent Ratio of Area Under the Curve From Time Zero to Last Quantifiable Concentration for Crizotinib Metabolite Ratio (MRAUClast) | 0.148 Ratio | Standard Deviation 0.021 |
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, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A and 0 (pre-dose), 1, 2, 4, 5, 6, 8, 10, 12, 24, 36, 48, 72, 96, and 144 hrs post oral crizotinib dose in Treatment B
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 50 mg IV | Plasma Decay Half Life (t1/2) | 38.86 hr | Standard Deviation 6.1 |
| Crizotinib 250 mg Oral | Plasma Decay Half Life (t1/2) | 28.98 hr | Standard Deviation 2.96 |
Secondary
Systemic Clearance (CL)
CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A
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 50 mg IV | Systemic Clearance (CL) | 46.83 L/hr | Standard Deviation 8.64 |
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 oral crizotinib dose in Treatment B
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 50 mg IV | Time to Reach Maximum Observed Plasma Concentration (Tmax) | 5.0 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 oral crizotinib dose in Treatment B
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 50 mg IV | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Crizotinib Metabolite (PF-06260182) | 5.00 hr |
Secondary
Volume of Distribution at Steady State (Vss)
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. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state.
Time frame: 0 (pre-dose), 1, 2, 2.5, 3, 4, 6, 8, 12, 24, 36, 48, 72, 96, and 144 hrs post IV crizotinib dose in Treatment A
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 50 mg IV | Volume of Distribution at Steady State (Vss) | 1772.00 L | Standard Deviation 328.75 |