Hematologic Malignancies
Conditions
Keywords
Chronic Myeloid Leukemia Myelofibrosis Myelodysplastic Syndrome Acute myeloid Leukemia Hedgehog inhibitor
Brief summary
This study examines the effect of a small molecule inhibitor to the Sonic Hedgehog pathway on select hematologic malignancies.
Interventions
DRUGPF-04449913
Escalating doses of PF-04449913 administered as tablets PO QD continuously in 28 day cycles
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with select advanced hematologic malignancies who are refractory, resistant or intolerant to prior therapies. They may be newly diagnosed and previously untreated, but not eligible for standard treatment options, or for whom standard therapies are not anticipated to result in a durable response. * ECOG performance status 0 to 2 * Adequate organ function
Exclusion criteria
* Patients with active CNS disease * Patient with active malignancy with the exception of basal cell carcinoma, non melanoma skin cancer, carcinoma in situ cervical or skin cancer * Active GVHD other than Grade 1 skin involvement * Known malabsorption syndrome * Patient has an active, life threatening or clinically significant uncontrolled systemic infection
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) | Cycle 1 Day 1 to end of Cycle 1 (28 days) | Any DLT event in Cycle 1: 1) Grade \>=3 non-hematologic toxicity that had been maximally treated, 2) prolonged myelosupression that lasted greater than (\>) 42 days from the point of detection in a normal bone marrow (less than \[\<\] 500 per microliter \[/uL\] or platelet count \<10,000/uL, or hemoglobin \<8 gram per deciliter \[g/dL\] with \<5% blasts and no evidence of disease or dysplasia), 3) inability to deliver \>= 80% of the planned doses due to PF-04449913 related non-hematologic and hematologic toxicities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Baseline up to 28 days post last dose of study medication (maximum duration: 537 days) | An AE was any untoward medical occurrence in a participant. Treatment-related AEs are events that were assessed by the investigator as related to study medication. If the same participant in a given treatment had more than 1 occurrence in the same preferred term event category, only the worst CTCAE grade (1 = mild AE, 2 = moderate AE, 3 = severe AE, 4 = life-threatening or disabling AE, 5 = death related to AE) was reported. |
| Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Screening up to maximum of 537 days | Participants with systolic blood pressure (BP) less than (\<) 90 millimeters of mercury (mmHg), maximum increase and decrease from baseline systolic BP of more than or equal to (\>=) 30 mmHg, diastolic BP \<50 mmHg, maximum increase and decrease from baseline diastolic BP \>=20 mmHg, and a heart rate of more than (\>) 120 beats per minute (bpm) at any time post dose were summarized. |
| Number of Participants With Laboratory Test Abnormalities | Screening to EOT (maximum duration: 537 days) | Number of participants with laboratory test abnormalities without regard to baseline abnormality as per the pre defined criteria were reported. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick and microscopy). |
| Hedgehog Biomarker Modulation: Relative GLI1 Gene Expression to Baseline for Normal Skin on Cycle 1 Day 21 | Baseline, Cycle 1 Day 21 | Ribonucleic acid (RNA) was extracted from skin samples and complementary deoxyribonucleic acid (cDNA) was prepared. Gene expression was measured using custom Taqman low density array (TLDA) cards run on the Applied Biosystems ViiATM 7 system. |
| Maximum Observed Plasma Concentration (Cmax) on Lead-in | Pre-dose, 0.5, 1, 2, 4, 8, 24, 48, 96 and 120 hours post-dose during the lead-in period (Day -6) | — |
| Maximum Observed Plasma Concentration (Cmax) on Cycle 1 Day 21 | Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21 | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) on Lead-in | Pre-dose, 0.5, 1, 2, 4, 8, 24, 48, 96 and 120 hours post-dose during the lead-in period (Day -6) | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) on Cycle 1 Day 21 | Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21 | — |
| Apparent Oral Clearance (CL/F) on Lead-in | Pre-dose, 0.5, 1, 2, 4, 8, 24, 48, 96 and 120 hours post-dose during the lead-in period (Day -6) | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Apparent Oral Clearance (CL/F) on Cycle 1 Day 21 | Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Apparent Volume of Distribution (Vz/F) on Lead-in | Pre-dose, 0.5, 1, 2, 4, 8, 24, 48, 96 and 120 hours post-dose during the lead-in period (Day -6) | 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. |
| Plasma Decay Half-life (t1/2) on Lead-in | Pre-dose, 0.5, 1, 2, 4, 8, 24, 48, 96 and 120 hours post-dose during the lead-in period (Day -6) | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUCinf) on Lead-in | Pre-dose, 0.5, 1, 2, 4, 8, 24, 48, 96 and 120 hours post-dose during the lead-in period (Day -6) | — |
| Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Cycle 1 Day 21 | Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21 | — |
| Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Baseline up to 28 days post last dose of study medication (maximum duration: 537 days) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs are events which occurred between first dose of study drug and 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. If the same participant in a given treatment had more than 1 occurrence in the same preferred term event category, only the worst CTCAE grade (1 = mild AE, 2 = moderate AE, 3 = severe AE, 4 = life-threatening or disabling AE, 5 = death related to AE) was reported. |
| Minimum Plasma Concentration (Cmin) on Cycle 1 Day 21 | Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21 | — |
| Pre-dose Concentration (Ctrough) on Cycle 1 Day 21 | Pre-dose on Cycle 1 Day 21 | — |
| Accumulation Ratio (Rac) | Pre-dose, 1 hour post-dose on Cycle 1 Day 1; Pre-dose, 0.5, 1, 2, 4, 8 and 24 hours post-dose on Cycle 1 Day 21 | Accumulation ratio was calculated as AUCtau at steady state (Cycle 1/Day 21)/AUCtau on Cycle 1 Day 1. |
| Linearity Ratio (Rss) | Pre-dose, 0.5, 1, 2, 4, 8, 24, 48, 96, 120 hours post-dose during the lead-in period (Day -6); Pre-dose, 0.5, 1, 2, 4, 8 and 24 hours post-dose on Cycle 1 Day 21 | Linearity ratio was calculated as AUCtau at steady state (Cycle 1/Day 21)/AUCinf after single dose (Lead-in Period \[Day -6\]). |
| Renal Clearance on Cycle 1 Day 21 | Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21 | Renal clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by the kidneys. |
| Amount of Unchanged Drug Excreted in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21 | — |
| Percentage of Dose Excreted Unchanged in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21 | — |
| Percentage of Participants With Objective Response (OR) | Baseline to end of study (up to 537 days) | Percentage of participants with OR based on assessment of disease response according to disease specific response criteria (hematologic, cytogenetic and molecular responses). Results were analyzed based on malignancies, according to the planned analysis. |
| Time to Progression (TTP) | Baseline to end of study, up to 36 months | Time in months from start of study treatment to first documentation of objective disease progression or death due to cancer, whichever comes first. TTP was calculated as (first event date - date of first dose of study medication + 1)/30.4. Disease progression was determined from oncologic assessment data (where data met the criteria for disease progression: categorized as early progressor from chronic phase \[CP\], progressor to accelerated phase \[AP\] or blast crisis \[BC\] from CP or return to CP, progressor to AP to BC, loss of confirmed complete hematologic response, or loss of major cytogenetic response). |
| Duration of Response (DR) | Baseline to end of study, up to 36 months | Time in months from the first documentation of objective response to objective disease progression or death due to any cancer. DR was calculated as \[date of first documentation of progression or death due to cancer - date of first disease response + 1\]/30.4. DR was calculated for the subgroup of participants with an objective disease response. |
| Progression-Free Survival (PFS) | Baseline to end of study, up to 36 months | Time in months from start of study treatment to first documentation of objective disease progression or death due to any cause. PFS was calculated as \[first event date - date of first dose of study medication + 1\]/30.4. Disease progression was determined from oncologic assessment data (where data met the criteria for disease progression: categorized as early progressor from CP, progressor to AP or BC from CP or return to CP, progressor to AP to BC, loss of confirmed complete hematologic response, or loss of major cytogenetic response; or from adverse event data (where the outcome was Death). |
| Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | Screening; predose, 1, 4, 24 hours (hr) postdose on Day -6; predose, 1 hr postdose on Cycle 1 Day 1; 1 hr postdose on Cycle 1 Days 8, 15; Day 1 of every subsequent cycle; predose, 1, 2, 4, 24 hr postdose for Cycle 1 Day 21; EOT (max reached: Cycle 20) | Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and the average was calculated. The time from ECG Q wave to the end of the T wave corresponding to electrical systole (QT) was corrected for heart rate (QTc). QTc using Fridericia's formula (QTcF) was calculated. Participants with maximum increase from baseline of \<30 millisecond (msec), 30 to \<60 msec and \>=60 msec were summarized. |
| Number of Participants With Decrease From Baseline in QTcF Interval | Baseline up to maximum of 537 days | Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and the average was calculated. QTcF was calculated. Participants with maximum decrease from baseline of \<30 msec, 30 to \<60 msec and \>=60 msec were summarized. |
| Number of Participants With Post-baseline QTcF Interval >= 500 Msec | Baseline up to maximum of 537 days | Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and the average was calculated. QTcF was calculated. Participants with post-baseline absolute QTcF values \>=500 msec were summarized. |
| Average Plasma Concentration (Cavg) on Cycle 1 Day 21 | Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21 | — |
Countries
Italy, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PF-04449913 5 mg Participants received oral single agent PF-04449913 tablets 5 milligram (mg) once on Day -6 (as a lead-in dose), followed by once daily (QD) dosing starting from Cycle 1 Day 1, without interruption, in 28-day cycles (maximum duration: 537 days). | 3 |
| PF-04449913 10 mg Participants received oral single agent PF-04449913 tablets 10 mg once on Day -6 (as a lead-in dose), followed by QD dosing from Cycle 1 Day 1, without interruption, in 28-day cycles (maximum duration: 537 days). | 3 |
| PF-04449913 20 mg Participants received oral single agent PF-04449913 tablets 20 mg once on Day -6 (as a lead-in dose), followed by QD dosing starting from Cycle 1 Day 1, without interruption, in 28-day cycles (maximum duration: 537 days). | 4 |
| PF-04449913 40 mg Participants received oral single agent PF-04449913 tablets 40 mg once on Day -6 (as a lead-in dose), followed by QD dosing starting from Cycle 1 Day 1, without interruption, in 28-day cycles (maximum duration: 537 days). | 4 |
| PF-04449913 80 mg Participants received oral single agent PF-04449913 tablets 80 mg once on Day -6 (as a lead-in dose), followed by QD dosing starting from Cycle 1 Day 1, without interruption, in 28-day cycles (maximum duration: 537 days). | 8 |
| PF-04449913 120 mg Participants received oral single agent PF-04449913 tablets 120 mg once on Day -6 (as a lead-in dose), followed by QD dosing starting from Cycle 1 Day 1, without interruption, in 28-day cycles (maximum duration: 537 days). | 3 |
| PF-04449913 180 mg Participants received oral single agent PF-04449913 tablets 180 mg once on Day -6 (as a lead-in dose), followed by QD dosing starting from Cycle 1 Day 1, without interruption, in 28-day cycles (maximum duration: 537 days). | 3 |
| PF-04449913 270 mg Participants received oral single agent PF-04449913 tablets 270 mg once on Day -6 (as a lead-in dose), followed by QD dosing starting from Cycle 1 Day 1, without interruption, in 28-day cycles (maximum duration: 537 days). | 5 |
| PF-04449913 400 mg Participants received oral single agent PF-04449913 tablets 400 mg once on Day -6 (as a lead-in dose), followed by QD dosing starting from Cycle 1 Day 1, without interruption, in 28-day cycles (maximum duration: 537 days). | 9 |
| PF-04449913 600 mg Participants received oral single agent PF-04449913 tablets 600 mg once on Day -6 (as a lead-in dose), followed by QD dosing starting from Cycle 1 Day 1, without interruption, in 28-day cycles (maximum duration: 537 days). | 5 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 0 | 1 | 1 | 1 | 1 | 1 | 3 | 1 | 0 |
| Overall Study | Disease progression | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Participant refused further follow-up | 0 | 0 | 1 | 0 | 3 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Participant went for transplant | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | PF-04449913 5 mg | PF-04449913 10 mg | PF-04449913 20 mg | PF-04449913 40 mg | PF-04449913 80 mg | PF-04449913 120 mg | PF-04449913 180 mg | PF-04449913 270 mg | PF-04449913 400 mg | PF-04449913 600 mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 3 Participants | 3 Participants | 3 Participants | 6 Participants | 1 Participants | 2 Participants | 3 Participants | 4 Participants | 5 Participants | 32 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 1 Participants | 2 Participants | 5 Participants | 0 Participants | 15 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 3 Participants | 2 Participants | 3 Participants | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 3 Participants | 19 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 5 Participants | 2 Participants | 3 Participants | 3 Participants | 7 Participants | 2 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 4 / 4 | 4 / 4 | 8 / 8 | 3 / 3 | 3 / 3 | 5 / 5 | 9 / 9 | 5 / 5 |
| serious Total, serious adverse events | 2 / 3 | 2 / 3 | 2 / 4 | 3 / 4 | 5 / 8 | 2 / 3 | 2 / 3 | 3 / 5 | 8 / 9 | 3 / 5 |
Outcome results
Primary
Number of Participants With First Cycle Dose-limiting Toxicities (DLTs)
Any DLT event in Cycle 1: 1) Grade \>=3 non-hematologic toxicity that had been maximally treated, 2) prolonged myelosupression that lasted greater than (\>) 42 days from the point of detection in a normal bone marrow (less than \[\<\] 500 per microliter \[/uL\] or platelet count \<10,000/uL, or hemoglobin \<8 gram per deciliter \[g/dL\] with \<5% blasts and no evidence of disease or dysplasia), 3) inability to deliver \>= 80% of the planned doses due to PF-04449913 related non-hematologic and hematologic toxicities
Time frame: Cycle 1 Day 1 to end of Cycle 1 (28 days)
Population: Only participants who did not have major treatment deviations in Cycle 1 were evaluable for DLT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-04449913 5 mg | Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) | 0 Participants |
| PF-04449913 10 mg | Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) | 0 Participants |
| PF-04449913 20 mg | Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) | 0 Participants |
| PF-04449913 40 mg | Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) | 0 Participants |
| PF-04449913 80 mg | Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) | 1 Participants |
| PF-04449913 120 mg | Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) | 0 Participants |
| PF-04449913 180 mg | Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) | 0 Participants |
| PF-04449913 270 mg | Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) | 0 Participants |
| PF-04449913 400 mg | Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) | 0 Participants |
| PF-04449913 600 mg | Number of Participants With First Cycle Dose-limiting Toxicities (DLTs) | 1 Participants |
Secondary
Accumulation Ratio (Rac)
Accumulation ratio was calculated as AUCtau at steady state (Cycle 1/Day 21)/AUCtau on Cycle 1 Day 1.
Time frame: Pre-dose, 1 hour post-dose on Cycle 1 Day 1; Pre-dose, 0.5, 1, 2, 4, 8 and 24 hours post-dose on Cycle 1 Day 21
Population: PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest. N = the number of participants analyzed for Cycle 1. 1 participant from the 270-mg arm had dose reduction to 180 mg and is analyzed and reported under the 180-mg arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-04449913 5 mg | Accumulation Ratio (Rac) | 1.4 ratio |
| PF-04449913 10 mg | Accumulation Ratio (Rac) | 1.6 ratio |
| PF-04449913 20 mg | Accumulation Ratio (Rac) | 1.6 ratio |
| PF-04449913 40 mg | Accumulation Ratio (Rac) | 2.4 ratio |
| PF-04449913 80 mg | Accumulation Ratio (Rac) | 1.4 ratio |
| PF-04449913 120 mg | Accumulation Ratio (Rac) | 2.5 ratio |
| PF-04449913 180 mg | Accumulation Ratio (Rac) | 1.4 ratio |
| PF-04449913 270 mg | Accumulation Ratio (Rac) | 1.5 ratio |
| PF-04449913 400 mg | Accumulation Ratio (Rac) | 1.2 ratio |
| PF-04449913 600 mg | Accumulation Ratio (Rac) | 1.4 ratio |
Secondary
Amount of Unchanged Drug Excreted in Urine (Over the Dosing Interval) on Cycle 1 Day 21
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21
Population: The PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest. N = number of participants with available data for this PK parameter in this period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04449913 5 mg | Amount of Unchanged Drug Excreted in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 352 microgram (mcg) | — |
| PF-04449913 10 mg | Amount of Unchanged Drug Excreted in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 1027 microgram (mcg) | Geometric Coefficient of Variation 15 |
| PF-04449913 20 mg | Amount of Unchanged Drug Excreted in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 1933 microgram (mcg) | Geometric Coefficient of Variation 43 |
| PF-04449913 40 mg | Amount of Unchanged Drug Excreted in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 2357 microgram (mcg) | Geometric Coefficient of Variation 91 |
| PF-04449913 80 mg | Amount of Unchanged Drug Excreted in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 8524 microgram (mcg) | Geometric Coefficient of Variation 63 |
| PF-04449913 120 mg | Amount of Unchanged Drug Excreted in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 9066 microgram (mcg) | Geometric Coefficient of Variation 44 |
| PF-04449913 180 mg | Amount of Unchanged Drug Excreted in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 30180 microgram (mcg) | Geometric Coefficient of Variation 46 |
| PF-04449913 270 mg | Amount of Unchanged Drug Excreted in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 27710 microgram (mcg) | — |
| PF-04449913 400 mg | Amount of Unchanged Drug Excreted in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 44570 microgram (mcg) | Geometric Coefficient of Variation 38 |
| PF-04449913 600 mg | Amount of Unchanged Drug Excreted in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 77770 microgram (mcg) | Geometric Coefficient of Variation 85 |
Secondary
Apparent Oral Clearance (CL/F) on Cycle 1 Day 21
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21
Population: PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest. N = the number of participants analyzed for Cycle 1. 1 participant from the 270-mg arm had dose reduction to 180 mg and is analyzed and reported under the 180-mg arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04449913 5 mg | Apparent Oral Clearance (CL/F) on Cycle 1 Day 21 | 8.57 L/hour | Geometric Coefficient of Variation 9 |
| PF-04449913 10 mg | Apparent Oral Clearance (CL/F) on Cycle 1 Day 21 | 13.3 L/hour | Geometric Coefficient of Variation 27 |
| PF-04449913 20 mg | Apparent Oral Clearance (CL/F) on Cycle 1 Day 21 | 7.79 L/hour | Geometric Coefficient of Variation 13 |
| PF-04449913 40 mg | Apparent Oral Clearance (CL/F) on Cycle 1 Day 21 | 6.52 L/hour | Geometric Coefficient of Variation 62 |
| PF-04449913 80 mg | Apparent Oral Clearance (CL/F) on Cycle 1 Day 21 | 10.7 L/hour | Geometric Coefficient of Variation 46 |
| PF-04449913 120 mg | Apparent Oral Clearance (CL/F) on Cycle 1 Day 21 | 5.33 L/hour | Geometric Coefficient of Variation 13 |
| PF-04449913 180 mg | Apparent Oral Clearance (CL/F) on Cycle 1 Day 21 | 7.81 L/hour | Geometric Coefficient of Variation 48 |
| PF-04449913 270 mg | Apparent Oral Clearance (CL/F) on Cycle 1 Day 21 | 11.8 L/hour | — |
| PF-04449913 400 mg | Apparent Oral Clearance (CL/F) on Cycle 1 Day 21 | 5.68 L/hour | Geometric Coefficient of Variation 24 |
| PF-04449913 600 mg | Apparent Oral Clearance (CL/F) on Cycle 1 Day 21 | 8.36 L/hour | Geometric Coefficient of Variation 51 |
Secondary
Apparent Oral Clearance (CL/F) on Lead-in
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24, 48, 96 and 120 hours post-dose during the lead-in period (Day -6)
Population: The PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest. N = number of participants with available data for this PK parameter in this period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04449913 5 mg | Apparent Oral Clearance (CL/F) on Lead-in | 7.61 liter (L)/hour | Geometric Coefficient of Variation 19 |
| PF-04449913 10 mg | Apparent Oral Clearance (CL/F) on Lead-in | 12.7 liter (L)/hour | Geometric Coefficient of Variation 23 |
| PF-04449913 20 mg | Apparent Oral Clearance (CL/F) on Lead-in | 5.63 liter (L)/hour | Geometric Coefficient of Variation 50 |
| PF-04449913 40 mg | Apparent Oral Clearance (CL/F) on Lead-in | 11.1 liter (L)/hour | Geometric Coefficient of Variation 37 |
| PF-04449913 80 mg | Apparent Oral Clearance (CL/F) on Lead-in | 9.13 liter (L)/hour | Geometric Coefficient of Variation 64 |
| PF-04449913 120 mg | Apparent Oral Clearance (CL/F) on Lead-in | 8.33 liter (L)/hour | Geometric Coefficient of Variation 36 |
| PF-04449913 180 mg | Apparent Oral Clearance (CL/F) on Lead-in | 8.48 liter (L)/hour | Geometric Coefficient of Variation 64 |
| PF-04449913 270 mg | Apparent Oral Clearance (CL/F) on Lead-in | 10.8 liter (L)/hour | Geometric Coefficient of Variation 110 |
| PF-04449913 400 mg | Apparent Oral Clearance (CL/F) on Lead-in | 5.90 liter (L)/hour | Geometric Coefficient of Variation 19 |
| PF-04449913 600 mg | Apparent Oral Clearance (CL/F) on Lead-in | 6.93 liter (L)/hour | Geometric Coefficient of Variation 58 |
Secondary
Apparent Volume of Distribution (Vz/F) on Lead-in
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: Pre-dose, 0.5, 1, 2, 4, 8, 24, 48, 96 and 120 hours post-dose during the lead-in period (Day -6)
Population: The PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest. N = number of participants with available data for this PK parameter in this period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04449913 5 mg | Apparent Volume of Distribution (Vz/F) on Lead-in | 262 liter (L) | Geometric Coefficient of Variation 32 |
| PF-04449913 10 mg | Apparent Volume of Distribution (Vz/F) on Lead-in | 455 liter (L) | Geometric Coefficient of Variation 41 |
| PF-04449913 20 mg | Apparent Volume of Distribution (Vz/F) on Lead-in | 265 liter (L) | Geometric Coefficient of Variation 62 |
| PF-04449913 40 mg | Apparent Volume of Distribution (Vz/F) on Lead-in | 367 liter (L) | Geometric Coefficient of Variation 38 |
| PF-04449913 80 mg | Apparent Volume of Distribution (Vz/F) on Lead-in | 292 liter (L) | Geometric Coefficient of Variation 71 |
| PF-04449913 120 mg | Apparent Volume of Distribution (Vz/F) on Lead-in | 316 liter (L) | Geometric Coefficient of Variation 52 |
| PF-04449913 180 mg | Apparent Volume of Distribution (Vz/F) on Lead-in | 210 liter (L) | Geometric Coefficient of Variation 92 |
| PF-04449913 270 mg | Apparent Volume of Distribution (Vz/F) on Lead-in | 359 liter (L) | Geometric Coefficient of Variation 143 |
| PF-04449913 400 mg | Apparent Volume of Distribution (Vz/F) on Lead-in | 185 liter (L) | Geometric Coefficient of Variation 50 |
| PF-04449913 600 mg | Apparent Volume of Distribution (Vz/F) on Lead-in | 191 liter (L) | Geometric Coefficient of Variation 78 |
Secondary
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Cycle 1 Day 21
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21
Population: PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest. N = the number of participants analyzed for Cycle 1. 1 participant from the 270-mg arm had dose reduction to 180 mg and is analyzed and reported under the 180-mg arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04449913 5 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Cycle 1 Day 21 | 583 ng*hour/mL | Geometric Coefficient of Variation 10 |
| PF-04449913 10 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Cycle 1 Day 21 | 753 ng*hour/mL | Geometric Coefficient of Variation 27 |
| PF-04449913 20 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Cycle 1 Day 21 | 2566 ng*hour/mL | Geometric Coefficient of Variation 13 |
| PF-04449913 40 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Cycle 1 Day 21 | 6134 ng*hour/mL | Geometric Coefficient of Variation 61 |
| PF-04449913 80 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Cycle 1 Day 21 | 7482 ng*hour/mL | Geometric Coefficient of Variation 46 |
| PF-04449913 120 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Cycle 1 Day 21 | 22520 ng*hour/mL | Geometric Coefficient of Variation 13 |
| PF-04449913 180 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Cycle 1 Day 21 | 23060 ng*hour/mL | Geometric Coefficient of Variation 47 |
| PF-04449913 270 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Cycle 1 Day 21 | 22990 ng*hour/mL | — |
| PF-04449913 400 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Cycle 1 Day 21 | 70430 ng*hour/mL | Geometric Coefficient of Variation 24 |
| PF-04449913 600 mg | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Cycle 1 Day 21 | 71710 ng*hour/mL | Geometric Coefficient of Variation 51 |
Secondary
Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUCinf) on Lead-in
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24, 48, 96 and 120 hours post-dose during the lead-in period (Day -6)
Population: The PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest. N = number of participants with available data for this PK parameter in this period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04449913 5 mg | Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUCinf) on Lead-in | 657 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 19 |
| PF-04449913 10 mg | Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUCinf) on Lead-in | 786 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 23 |
| PF-04449913 20 mg | Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUCinf) on Lead-in | 3548 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 50 |
| PF-04449913 40 mg | Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUCinf) on Lead-in | 3614 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 38 |
| PF-04449913 80 mg | Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUCinf) on Lead-in | 8755 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 64 |
| PF-04449913 120 mg | Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUCinf) on Lead-in | 14430 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 35 |
| PF-04449913 180 mg | Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUCinf) on Lead-in | 21280 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 64 |
| PF-04449913 270 mg | Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUCinf) on Lead-in | 25110 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 109 |
| PF-04449913 400 mg | Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUCinf) on Lead-in | 67720 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 19 |
| PF-04449913 600 mg | Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUCinf) on Lead-in | 86620 nanograms*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 58 |
Secondary
Average Plasma Concentration (Cavg) on Cycle 1 Day 21
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21
Population: PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest. N = the number of participants analyzed for Cycle 1. 1 participant from the 270-mg arm had dose reduction to 180 mg and is analyzed and reported under the 180-mg arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04449913 5 mg | Average Plasma Concentration (Cavg) on Cycle 1 Day 21 | 24.3 ng/mL | Geometric Coefficient of Variation 9 |
| PF-04449913 10 mg | Average Plasma Concentration (Cavg) on Cycle 1 Day 21 | 31.4 ng/mL | Geometric Coefficient of Variation 27 |
| PF-04449913 20 mg | Average Plasma Concentration (Cavg) on Cycle 1 Day 21 | 107 ng/mL | Geometric Coefficient of Variation 13 |
| PF-04449913 40 mg | Average Plasma Concentration (Cavg) on Cycle 1 Day 21 | 256 ng/mL | Geometric Coefficient of Variation 61 |
| PF-04449913 80 mg | Average Plasma Concentration (Cavg) on Cycle 1 Day 21 | 312 ng/mL | Geometric Coefficient of Variation 46 |
| PF-04449913 120 mg | Average Plasma Concentration (Cavg) on Cycle 1 Day 21 | 940 ng/mL | Geometric Coefficient of Variation 13 |
| PF-04449913 180 mg | Average Plasma Concentration (Cavg) on Cycle 1 Day 21 | 961 ng/mL | Geometric Coefficient of Variation 48 |
| PF-04449913 270 mg | Average Plasma Concentration (Cavg) on Cycle 1 Day 21 | 960 ng/mL | — |
| PF-04449913 400 mg | Average Plasma Concentration (Cavg) on Cycle 1 Day 21 | 2933 ng/mL | Geometric Coefficient of Variation 24 |
| PF-04449913 600 mg | Average Plasma Concentration (Cavg) on Cycle 1 Day 21 | 2986 ng/mL | Geometric Coefficient of Variation 51 |
Secondary
Duration of Response (DR)
Time in months from the first documentation of objective response to objective disease progression or death due to any cancer. DR was calculated as \[date of first documentation of progression or death due to cancer - date of first disease response + 1\]/30.4. DR was calculated for the subgroup of participants with an objective disease response.
Time frame: Baseline to end of study, up to 36 months
Population: The Efficacy Analysis Set consisted of all enrolled participants who received Cycle 1 Day 1 dose of PF-04449913.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-04449913 5 mg | Duration of Response (DR) | 21.45 months |
| PF-04449913 10 mg | Duration of Response (DR) | NA months |
| PF-04449913 20 mg | Duration of Response (DR) | 2.83 months |
| PF-04449913 40 mg | Duration of Response (DR) | NA months |
| PF-04449913 80 mg | Duration of Response (DR) | NA months |
Secondary
Hedgehog Biomarker Modulation: Relative GLI1 Gene Expression to Baseline for Normal Skin on Cycle 1 Day 21
Ribonucleic acid (RNA) was extracted from skin samples and complementary deoxyribonucleic acid (cDNA) was prepared. Gene expression was measured using custom Taqman low density array (TLDA) cards run on the Applied Biosystems ViiATM 7 system.
Time frame: Baseline, Cycle 1 Day 21
Population: The pharmacodynamic (PD) analysis population included all enrolled participants who received at least 1 dose of PF-04449913 and had at least 1 PD parameter in at least 1 treatment period. Results were not collected and reported for the other reporting arms since none of the participants in those arms had evaluable PD samples.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-04449913 5 mg | Hedgehog Biomarker Modulation: Relative GLI1 Gene Expression to Baseline for Normal Skin on Cycle 1 Day 21 | 0.1 ratio |
| PF-04449913 10 mg | Hedgehog Biomarker Modulation: Relative GLI1 Gene Expression to Baseline for Normal Skin on Cycle 1 Day 21 | 0.0 ratio |
| PF-04449913 20 mg | Hedgehog Biomarker Modulation: Relative GLI1 Gene Expression to Baseline for Normal Skin on Cycle 1 Day 21 | 0.0 ratio |
Secondary
Linearity Ratio (Rss)
Linearity ratio was calculated as AUCtau at steady state (Cycle 1/Day 21)/AUCinf after single dose (Lead-in Period \[Day -6\]).
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24, 48, 96, 120 hours post-dose during the lead-in period (Day -6); Pre-dose, 0.5, 1, 2, 4, 8 and 24 hours post-dose on Cycle 1 Day 21
Population: PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest. N = the number of participants analyzed for Cycle 1. 1 participant from the 270-mg arm had dose reduction to 180 mg and is analyzed and reported under the 180-mg arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-04449913 5 mg | Linearity Ratio (Rss) | 0.91 ratio |
| PF-04449913 10 mg | Linearity Ratio (Rss) | 1.1 ratio |
| PF-04449913 20 mg | Linearity Ratio (Rss) | 0.76 ratio |
| PF-04449913 40 mg | Linearity Ratio (Rss) | 1.6 ratio |
| PF-04449913 80 mg | Linearity Ratio (Rss) | 0.97 ratio |
| PF-04449913 120 mg | Linearity Ratio (Rss) | 2.1 ratio |
| PF-04449913 180 mg | Linearity Ratio (Rss) | 1.0 ratio |
| PF-04449913 270 mg | Linearity Ratio (Rss) | 1.0 ratio |
| PF-04449913 400 mg | Linearity Ratio (Rss) | 0.86 ratio |
| PF-04449913 600 mg | Linearity Ratio (Rss) | 0.97 ratio |
Secondary
Maximum Observed Plasma Concentration (Cmax) on Cycle 1 Day 21
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21
Population: PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest. N = the number of participants analyzed for Cycle 1. 1 participant from the 270-mg arm had dose reduction to 180 mg and is analyzed and reported under the 180-mg arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04449913 5 mg | Maximum Observed Plasma Concentration (Cmax) on Cycle 1 Day 21 | 45.4 ng/mL | Geometric Coefficient of Variation 12 |
| PF-04449913 10 mg | Maximum Observed Plasma Concentration (Cmax) on Cycle 1 Day 21 | 75.0 ng/mL | Geometric Coefficient of Variation 30 |
| PF-04449913 20 mg | Maximum Observed Plasma Concentration (Cmax) on Cycle 1 Day 21 | 249 ng/mL | Geometric Coefficient of Variation 35 |
| PF-04449913 40 mg | Maximum Observed Plasma Concentration (Cmax) on Cycle 1 Day 21 | 565 ng/mL | Geometric Coefficient of Variation 83 |
| PF-04449913 80 mg | Maximum Observed Plasma Concentration (Cmax) on Cycle 1 Day 21 | 871 ng/mL | Geometric Coefficient of Variation 35 |
| PF-04449913 120 mg | Maximum Observed Plasma Concentration (Cmax) on Cycle 1 Day 21 | 1621 ng/mL | Geometric Coefficient of Variation 10 |
| PF-04449913 180 mg | Maximum Observed Plasma Concentration (Cmax) on Cycle 1 Day 21 | 2069 ng/mL | Geometric Coefficient of Variation 41 |
| PF-04449913 270 mg | Maximum Observed Plasma Concentration (Cmax) on Cycle 1 Day 21 | 1504 ng/mL | — |
| PF-04449913 400 mg | Maximum Observed Plasma Concentration (Cmax) on Cycle 1 Day 21 | 4989 ng/mL | Geometric Coefficient of Variation 7 |
| PF-04449913 600 mg | Maximum Observed Plasma Concentration (Cmax) on Cycle 1 Day 21 | 6413 ng/mL | Geometric Coefficient of Variation 65 |
Secondary
Maximum Observed Plasma Concentration (Cmax) on Lead-in
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24, 48, 96 and 120 hours post-dose during the lead-in period (Day -6)
Population: The pharmacokinetic (PK) analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04449913 5 mg | Maximum Observed Plasma Concentration (Cmax) on Lead-in | 32.9 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 3 |
| PF-04449913 10 mg | Maximum Observed Plasma Concentration (Cmax) on Lead-in | 59.0 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 21 |
| PF-04449913 20 mg | Maximum Observed Plasma Concentration (Cmax) on Lead-in | 247 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 47 |
| PF-04449913 40 mg | Maximum Observed Plasma Concentration (Cmax) on Lead-in | 313 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 51 |
| PF-04449913 80 mg | Maximum Observed Plasma Concentration (Cmax) on Lead-in | 746 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 56 |
| PF-04449913 120 mg | Maximum Observed Plasma Concentration (Cmax) on Lead-in | 1418 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 22 |
| PF-04449913 180 mg | Maximum Observed Plasma Concentration (Cmax) on Lead-in | 1409 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 79 |
| PF-04449913 270 mg | Maximum Observed Plasma Concentration (Cmax) on Lead-in | 1534 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 72 |
| PF-04449913 400 mg | Maximum Observed Plasma Concentration (Cmax) on Lead-in | 3714 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 30 |
| PF-04449913 600 mg | Maximum Observed Plasma Concentration (Cmax) on Lead-in | 4527 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 64 |
Secondary
Minimum Plasma Concentration (Cmin) on Cycle 1 Day 21
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21
Population: PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest. N = the number of participants analyzed for Cycle 1. 1 participant from the 270-mg arm had dose reduction to 180 mg and is analyzed and reported under the 180-mg arm.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04449913 5 mg | Minimum Plasma Concentration (Cmin) on Cycle 1 Day 21 | 14.7 ng/mL | Geometric Coefficient of Variation 15 |
| PF-04449913 10 mg | Minimum Plasma Concentration (Cmin) on Cycle 1 Day 21 | 18.9 ng/mL | Geometric Coefficient of Variation 14 |
| PF-04449913 20 mg | Minimum Plasma Concentration (Cmin) on Cycle 1 Day 21 | 54.7 ng/mL | Geometric Coefficient of Variation 46 |
| PF-04449913 40 mg | Minimum Plasma Concentration (Cmin) on Cycle 1 Day 21 | 162 ng/mL | Geometric Coefficient of Variation 107 |
| PF-04449913 80 mg | Minimum Plasma Concentration (Cmin) on Cycle 1 Day 21 | 116 ng/mL | Geometric Coefficient of Variation 48 |
| PF-04449913 120 mg | Minimum Plasma Concentration (Cmin) on Cycle 1 Day 21 | 360 ng/mL | Geometric Coefficient of Variation 115 |
| PF-04449913 180 mg | Minimum Plasma Concentration (Cmin) on Cycle 1 Day 21 | 408 ng/mL | Geometric Coefficient of Variation 42 |
| PF-04449913 270 mg | Minimum Plasma Concentration (Cmin) on Cycle 1 Day 21 | 428 ng/mL | — |
| PF-04449913 400 mg | Minimum Plasma Concentration (Cmin) on Cycle 1 Day 21 | 1113 ng/mL | Geometric Coefficient of Variation 44 |
| PF-04449913 600 mg | Minimum Plasma Concentration (Cmin) on Cycle 1 Day 21 | 1641 ng/mL | Geometric Coefficient of Variation 59 |
Secondary
Number of Participants With Decrease From Baseline in QTcF Interval
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and the average was calculated. QTcF was calculated. Participants with maximum decrease from baseline of \<30 msec, 30 to \<60 msec and \>=60 msec were summarized.
Time frame: Baseline up to maximum of 537 days
Population: QTc analysis set included all enrolled participants who had at least 1 ECG assessment after receiving at least 1 dose of PF-04449913.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-04449913 5 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: <30 msec | 1 Participants |
| PF-04449913 5 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: >=60 msec | 0 Participants |
| PF-04449913 5 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: 30-<60 msec | 1 Participants |
| PF-04449913 10 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: 30-<60 msec | 1 Participants |
| PF-04449913 10 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: >=60 msec | 0 Participants |
| PF-04449913 10 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: <30 msec | 2 Participants |
| PF-04449913 20 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: >=60 msec | 0 Participants |
| PF-04449913 20 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: <30 msec | 2 Participants |
| PF-04449913 20 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: 30-<60 msec | 2 Participants |
| PF-04449913 40 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: >=60 msec | 0 Participants |
| PF-04449913 40 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: <30 msec | 1 Participants |
| PF-04449913 40 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: 30-<60 msec | 3 Participants |
| PF-04449913 80 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: <30 msec | 5 Participants |
| PF-04449913 80 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: 30-<60 msec | 3 Participants |
| PF-04449913 80 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: >=60 msec | 0 Participants |
| PF-04449913 120 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: 30-<60 msec | 0 Participants |
| PF-04449913 120 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: <30 msec | 2 Participants |
| PF-04449913 120 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: >=60 msec | 1 Participants |
| PF-04449913 180 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: <30 msec | 3 Participants |
| PF-04449913 180 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: >=60 msec | 0 Participants |
| PF-04449913 180 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: 30-<60 msec | 0 Participants |
| PF-04449913 270 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: 30-<60 msec | 2 Participants |
| PF-04449913 270 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: <30 msec | 1 Participants |
| PF-04449913 270 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: >=60 msec | 1 Participants |
| PF-04449913 400 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: 30-<60 msec | 0 Participants |
| PF-04449913 400 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: <30 msec | 9 Participants |
| PF-04449913 400 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: >=60 msec | 0 Participants |
| PF-04449913 600 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: <30 msec | 4 Participants |
| PF-04449913 600 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: >=60 msec | 0 Participants |
| PF-04449913 600 mg | Number of Participants With Decrease From Baseline in QTcF Interval | QTcF, maximum decrease from baseline: 30-<60 msec | 0 Participants |
Secondary
Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF)
Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and the average was calculated. The time from ECG Q wave to the end of the T wave corresponding to electrical systole (QT) was corrected for heart rate (QTc). QTc using Fridericia's formula (QTcF) was calculated. Participants with maximum increase from baseline of \<30 millisecond (msec), 30 to \<60 msec and \>=60 msec were summarized.
Time frame: Screening; predose, 1, 4, 24 hours (hr) postdose on Day -6; predose, 1 hr postdose on Cycle 1 Day 1; 1 hr postdose on Cycle 1 Days 8, 15; Day 1 of every subsequent cycle; predose, 1, 2, 4, 24 hr postdose for Cycle 1 Day 21; EOT (max reached: Cycle 20)
Population: QTc analysis set included all enrolled participants who had at least 1 ECG assessment after receiving at least 1 dose of PF-04449913.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-04449913 5 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: 30-<60 msec | 0 Participants |
| PF-04449913 5 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: <30 msec | 2 Participants |
| PF-04449913 5 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: >=60 msec | 1 Participants |
| PF-04449913 10 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: <30 msec | 3 Participants |
| PF-04449913 10 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: >=60 msec | 0 Participants |
| PF-04449913 10 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: 30-<60 msec | 0 Participants |
| PF-04449913 20 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: <30 msec | 3 Participants |
| PF-04449913 20 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: 30-<60 msec | 1 Participants |
| PF-04449913 20 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: >=60 msec | 0 Participants |
| PF-04449913 40 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: >=60 msec | 0 Participants |
| PF-04449913 40 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: 30-<60 msec | 0 Participants |
| PF-04449913 40 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: <30 msec | 4 Participants |
| PF-04449913 80 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: <30 msec | 7 Participants |
| PF-04449913 80 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: >=60 msec | 0 Participants |
| PF-04449913 80 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: 30-<60 msec | 1 Participants |
| PF-04449913 120 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: <30 msec | 2 Participants |
| PF-04449913 120 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: 30-<60 msec | 1 Participants |
| PF-04449913 120 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: >=60 msec | 0 Participants |
| PF-04449913 180 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: <30 msec | 1 Participants |
| PF-04449913 180 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: >=60 msec | 0 Participants |
| PF-04449913 180 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: 30-<60 msec | 2 Participants |
| PF-04449913 270 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: <30 msec | 2 Participants |
| PF-04449913 270 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: 30-<60 msec | 3 Participants |
| PF-04449913 270 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: >=60 msec | 0 Participants |
| PF-04449913 400 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: 30-<60 msec | 7 Participants |
| PF-04449913 400 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: <30 msec | 2 Participants |
| PF-04449913 400 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: >=60 msec | 0 Participants |
| PF-04449913 600 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: >=60 msec | 5 Participants |
| PF-04449913 600 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: <30 msec | 0 Participants |
| PF-04449913 600 mg | Number of Participants With Increase From Baseline in Corrected QT Interval Using Fridericia's Formula (QTcF) | QTcF, maximum increase from baseline: 30-<60 msec | 0 Participants |
Secondary
Number of Participants With Laboratory Test Abnormalities
Number of participants with laboratory test abnormalities without regard to baseline abnormality as per the pre defined criteria were reported. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick and microscopy).
Time frame: Screening to EOT (maximum duration: 537 days)
Population: The safety analysis set consisted of all enrolled participants who received at least 1 dose of PF-04449913, including the lead-in dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-04449913 5 mg | Number of Participants With Laboratory Test Abnormalities | 3 Participants |
| PF-04449913 10 mg | Number of Participants With Laboratory Test Abnormalities | 3 Participants |
| PF-04449913 20 mg | Number of Participants With Laboratory Test Abnormalities | 4 Participants |
| PF-04449913 40 mg | Number of Participants With Laboratory Test Abnormalities | 4 Participants |
| PF-04449913 80 mg | Number of Participants With Laboratory Test Abnormalities | 8 Participants |
| PF-04449913 120 mg | Number of Participants With Laboratory Test Abnormalities | 3 Participants |
| PF-04449913 180 mg | Number of Participants With Laboratory Test Abnormalities | 3 Participants |
| PF-04449913 270 mg | Number of Participants With Laboratory Test Abnormalities | 5 Participants |
| PF-04449913 400 mg | Number of Participants With Laboratory Test Abnormalities | 9 Participants |
| PF-04449913 600 mg | Number of Participants With Laboratory Test Abnormalities | 5 Participants |
Secondary
Number of Participants With Post-baseline QTcF Interval >= 500 Msec
Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and the average was calculated. QTcF was calculated. Participants with post-baseline absolute QTcF values \>=500 msec were summarized.
Time frame: Baseline up to maximum of 537 days
Population: QTc analysis set included all enrolled participants who had at least 1 ECG assessment after receiving at least 1 dose of PF-04449913.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-04449913 5 mg | Number of Participants With Post-baseline QTcF Interval >= 500 Msec | 0 Participants |
| PF-04449913 10 mg | Number of Participants With Post-baseline QTcF Interval >= 500 Msec | 0 Participants |
| PF-04449913 20 mg | Number of Participants With Post-baseline QTcF Interval >= 500 Msec | 0 Participants |
| PF-04449913 40 mg | Number of Participants With Post-baseline QTcF Interval >= 500 Msec | 0 Participants |
| PF-04449913 80 mg | Number of Participants With Post-baseline QTcF Interval >= 500 Msec | 0 Participants |
| PF-04449913 120 mg | Number of Participants With Post-baseline QTcF Interval >= 500 Msec | 0 Participants |
| PF-04449913 180 mg | Number of Participants With Post-baseline QTcF Interval >= 500 Msec | 0 Participants |
| PF-04449913 270 mg | Number of Participants With Post-baseline QTcF Interval >= 500 Msec | 0 Participants |
| PF-04449913 400 mg | Number of Participants With Post-baseline QTcF Interval >= 500 Msec | 1 Participants |
| PF-04449913 600 mg | Number of Participants With Post-baseline QTcF Interval >= 500 Msec | 2 Participants |
Secondary
Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria
Participants with systolic blood pressure (BP) less than (\<) 90 millimeters of mercury (mmHg), maximum increase and decrease from baseline systolic BP of more than or equal to (\>=) 30 mmHg, diastolic BP \<50 mmHg, maximum increase and decrease from baseline diastolic BP \>=20 mmHg, and a heart rate of more than (\>) 120 beats per minute (bpm) at any time post dose were summarized.
Time frame: Screening up to maximum of 537 days
Population: The safety analysis set consisted of all enrolled participants who received at least 1 dose of PF-04449913, including the lead-in dose.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-04449913 5 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline diastolic BP >=20 mmHg | 1 Participants |
| PF-04449913 5 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Diastolic BP <50 mmHg | 1 Participants |
| PF-04449913 5 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Systolic BP <90 mmHg | 0 Participants |
| PF-04449913 5 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline systolic BP >=30 mmHg | 0 Participants |
| PF-04449913 5 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline diastolic BP >=20 mmHg | 1 Participants |
| PF-04449913 5 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Heart rate >120 bpm at any time post dose | 0 Participants |
| PF-04449913 5 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline systolic BP >=30 mmHg | 0 Participants |
| PF-04449913 10 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline diastolic BP >=20 mmHg | 0 Participants |
| PF-04449913 10 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline systolic BP >=30 mmHg | 1 Participants |
| PF-04449913 10 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Diastolic BP <50 mmHg | 0 Participants |
| PF-04449913 10 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Heart rate >120 bpm at any time post dose | 0 Participants |
| PF-04449913 10 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline diastolic BP >=20 mmHg | 0 Participants |
| PF-04449913 10 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Systolic BP <90 mmHg | 0 Participants |
| PF-04449913 10 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline systolic BP >=30 mmHg | 0 Participants |
| PF-04449913 20 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline diastolic BP >=20 mmHg | 2 Participants |
| PF-04449913 20 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Systolic BP <90 mmHg | 0 Participants |
| PF-04449913 20 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline systolic BP >=30 mmHg | 2 Participants |
| PF-04449913 20 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline diastolic BP >=20 mmHg | 1 Participants |
| PF-04449913 20 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Diastolic BP <50 mmHg | 1 Participants |
| PF-04449913 20 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline systolic BP >=30 mmHg | 1 Participants |
| PF-04449913 20 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Heart rate >120 bpm at any time post dose | 0 Participants |
| PF-04449913 40 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline systolic BP >=30 mmHg | 0 Participants |
| PF-04449913 40 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline systolic BP >=30 mmHg | 1 Participants |
| PF-04449913 40 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Systolic BP <90 mmHg | 0 Participants |
| PF-04449913 40 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline diastolic BP >=20 mmHg | 1 Participants |
| PF-04449913 40 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline diastolic BP >=20 mmHg | 0 Participants |
| PF-04449913 40 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Diastolic BP <50 mmHg | 2 Participants |
| PF-04449913 40 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Heart rate >120 bpm at any time post dose | 0 Participants |
| PF-04449913 80 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Diastolic BP <50 mmHg | 1 Participants |
| PF-04449913 80 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Systolic BP <90 mmHg | 1 Participants |
| PF-04449913 80 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Heart rate >120 bpm at any time post dose | 1 Participants |
| PF-04449913 80 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline systolic BP >=30 mmHg | 3 Participants |
| PF-04449913 80 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline diastolic BP >=20 mmHg | 0 Participants |
| PF-04449913 80 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline systolic BP >=30 mmHg | 0 Participants |
| PF-04449913 80 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline diastolic BP >=20 mmHg | 1 Participants |
| PF-04449913 120 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Diastolic BP <50 mmHg | 0 Participants |
| PF-04449913 120 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Systolic BP <90 mmHg | 0 Participants |
| PF-04449913 120 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline systolic BP >=30 mmHg | 1 Participants |
| PF-04449913 120 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline systolic BP >=30 mmHg | 1 Participants |
| PF-04449913 120 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline diastolic BP >=20 mmHg | 1 Participants |
| PF-04449913 120 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline diastolic BP >=20 mmHg | 0 Participants |
| PF-04449913 120 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Heart rate >120 bpm at any time post dose | 1 Participants |
| PF-04449913 180 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Diastolic BP <50 mmHg | 0 Participants |
| PF-04449913 180 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline diastolic BP >=20 mmHg | 0 Participants |
| PF-04449913 180 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline systolic BP >=30 mmHg | 1 Participants |
| PF-04449913 180 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline diastolic BP >=20 mmHg | 1 Participants |
| PF-04449913 180 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline systolic BP >=30 mmHg | 0 Participants |
| PF-04449913 180 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Systolic BP <90 mmHg | 0 Participants |
| PF-04449913 180 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Heart rate >120 bpm at any time post dose | 1 Participants |
| PF-04449913 270 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Systolic BP <90 mmHg | 0 Participants |
| PF-04449913 270 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Heart rate >120 bpm at any time post dose | 1 Participants |
| PF-04449913 270 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline diastolic BP >=20 mmHg | 2 Participants |
| PF-04449913 270 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Diastolic BP <50 mmHg | 0 Participants |
| PF-04449913 270 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline diastolic BP >=20 mmHg | 1 Participants |
| PF-04449913 270 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline systolic BP >=30 mmHg | 2 Participants |
| PF-04449913 270 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline systolic BP >=30 mmHg | 1 Participants |
| PF-04449913 400 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Systolic BP <90 mmHg | 1 Participants |
| PF-04449913 400 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Heart rate >120 bpm at any time post dose | 3 Participants |
| PF-04449913 400 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline systolic BP >=30 mmHg | 1 Participants |
| PF-04449913 400 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline systolic BP >=30 mmHg | 2 Participants |
| PF-04449913 400 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Diastolic BP <50 mmHg | 0 Participants |
| PF-04449913 400 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline diastolic BP >=20 mmHg | 3 Participants |
| PF-04449913 400 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline diastolic BP >=20 mmHg | 3 Participants |
| PF-04449913 600 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline diastolic BP >=20 mmHg | 1 Participants |
| PF-04449913 600 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Heart rate >120 bpm at any time post dose | 0 Participants |
| PF-04449913 600 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline systolic BP >=30 mmHg | 1 Participants |
| PF-04449913 600 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Decrease from baseline diastolic BP >=20 mmHg | 0 Participants |
| PF-04449913 600 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Diastolic BP <50 mmHg | 0 Participants |
| PF-04449913 600 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Systolic BP <90 mmHg | 0 Participants |
| PF-04449913 600 mg | Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria | Increase from baseline systolic BP >=30 mmHg | 1 Participants |
Secondary
Percentage of Dose Excreted Unchanged in Urine (Over the Dosing Interval) on Cycle 1 Day 21
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21
Population: The PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest. N = number of participants with available data for this PK parameter in this period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04449913 5 mg | Percentage of Dose Excreted Unchanged in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 7.03 Percentage of dose | — |
| PF-04449913 10 mg | Percentage of Dose Excreted Unchanged in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 10.3 Percentage of dose | Geometric Coefficient of Variation 15 |
| PF-04449913 20 mg | Percentage of Dose Excreted Unchanged in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 9.68 Percentage of dose | Geometric Coefficient of Variation 43 |
| PF-04449913 40 mg | Percentage of Dose Excreted Unchanged in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 5.89 Percentage of dose | Geometric Coefficient of Variation 91 |
| PF-04449913 80 mg | Percentage of Dose Excreted Unchanged in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 10.7 Percentage of dose | Geometric Coefficient of Variation 63 |
| PF-04449913 120 mg | Percentage of Dose Excreted Unchanged in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 7.57 Percentage of dose | Geometric Coefficient of Variation 44 |
| PF-04449913 180 mg | Percentage of Dose Excreted Unchanged in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 16.8 Percentage of dose | Geometric Coefficient of Variation 46 |
| PF-04449913 270 mg | Percentage of Dose Excreted Unchanged in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 10.3 Percentage of dose | — |
| PF-04449913 400 mg | Percentage of Dose Excreted Unchanged in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 11.1 Percentage of dose | Geometric Coefficient of Variation 38 |
| PF-04449913 600 mg | Percentage of Dose Excreted Unchanged in Urine (Over the Dosing Interval) on Cycle 1 Day 21 | 13.0 Percentage of dose | Geometric Coefficient of Variation 85 |
Secondary
Percentage of Participants With Objective Response (OR)
Percentage of participants with OR based on assessment of disease response according to disease specific response criteria (hematologic, cytogenetic and molecular responses). Results were analyzed based on malignancies, according to the planned analysis.
Time frame: Baseline to end of study (up to 537 days)
Population: The Efficacy Analysis Set consisted of all enrolled participants who received Cycle 1 Day 1 dose of PF-04449913.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-04449913 5 mg | Percentage of Participants With Objective Response (OR) | 28.6 Percentage of participants |
| PF-04449913 10 mg | Percentage of Participants With Objective Response (OR) | 28.6 Percentage of participants |
| PF-04449913 20 mg | Percentage of Participants With Objective Response (OR) | 32.1 Percentage of participants |
| PF-04449913 40 mg | Percentage of Participants With Objective Response (OR) | 0 Percentage of participants |
| PF-04449913 80 mg | Percentage of Participants With Objective Response (OR) | 0 Percentage of participants |
Secondary
Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs are events which occurred between first dose of study drug and 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. If the same participant in a given treatment had more than 1 occurrence in the same preferred term event category, only the worst CTCAE grade (1 = mild AE, 2 = moderate AE, 3 = severe AE, 4 = life-threatening or disabling AE, 5 = death related to AE) was reported.
Time frame: Baseline up to 28 days post last dose of study medication (maximum duration: 537 days)
Population: The safety analysis set consisted of all enrolled participants who received at least 1 dose of PF-04449913, including the lead-in dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04449913 5 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 4 | 66.7 percentage of participants |
| PF-04449913 5 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 5 | 33.3 percentage of participants |
| PF-04449913 5 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 1 | 0.0 percentage of participants |
| PF-04449913 5 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 3 | 0.0 percentage of participants |
| PF-04449913 5 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 2 | 0.0 percentage of participants |
| PF-04449913 10 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 5 | 0.0 percentage of participants |
| PF-04449913 10 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 2 | 0.0 percentage of participants |
| PF-04449913 10 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 3 | 66.7 percentage of participants |
| PF-04449913 10 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 1 | 0.0 percentage of participants |
| PF-04449913 10 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 4 | 33.3 percentage of participants |
| PF-04449913 20 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 2 | 0.0 percentage of participants |
| PF-04449913 20 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 5 | 12.5 percentage of participants |
| PF-04449913 20 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 1 | 0.0 percentage of participants |
| PF-04449913 20 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 4 | 25.0 percentage of participants |
| PF-04449913 20 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 3 | 50.0 percentage of participants |
| PF-04449913 40 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 4 | 25.0 percentage of participants |
| PF-04449913 40 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 1 | 0.0 percentage of participants |
| PF-04449913 40 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 5 | 25.0 percentage of participants |
| PF-04449913 40 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 2 | 25.0 percentage of participants |
| PF-04449913 40 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 3 | 25.0 percentage of participants |
| PF-04449913 80 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 2 | 12.5 percentage of participants |
| PF-04449913 80 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 5 | 12.5 percentage of participants |
| PF-04449913 80 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 4 | 25.0 percentage of participants |
| PF-04449913 80 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 1 | 0.0 percentage of participants |
| PF-04449913 80 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 3 | 50.0 percentage of participants |
| PF-04449913 120 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 3 | 33.3 percentage of participants |
| PF-04449913 120 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 1 | 0.0 percentage of participants |
| PF-04449913 120 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 2 | 33.3 percentage of participants |
| PF-04449913 120 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 4 | 0.0 percentage of participants |
| PF-04449913 120 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 5 | 33.3 percentage of participants |
| PF-04449913 180 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 2 | 33.3 percentage of participants |
| PF-04449913 180 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 4 | 0.0 percentage of participants |
| PF-04449913 180 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 5 | 0.0 percentage of participants |
| PF-04449913 180 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 1 | 0.0 percentage of participants |
| PF-04449913 180 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 3 | 66.7 percentage of participants |
| PF-04449913 270 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 3 | 20.0 percentage of participants |
| PF-04449913 270 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 2 | 40.0 percentage of participants |
| PF-04449913 270 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 4 | 0.0 percentage of participants |
| PF-04449913 270 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 1 | 0.0 percentage of participants |
| PF-04449913 270 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 5 | 40.0 percentage of participants |
| PF-04449913 400 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 1 | 0.0 percentage of participants |
| PF-04449913 400 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 3 | 55.6 percentage of participants |
| PF-04449913 400 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 2 | 0.0 percentage of participants |
| PF-04449913 400 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 4 | 22.2 percentage of participants |
| PF-04449913 400 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 5 | 22.2 percentage of participants |
| PF-04449913 600 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 4 | 40.0 percentage of participants |
| PF-04449913 600 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 1 | 0.0 percentage of participants |
| PF-04449913 600 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 5 | 0.0 percentage of participants |
| PF-04449913 600 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 2 | 40.0 percentage of participants |
| PF-04449913 600 mg | Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade | Any AEs, Grade 3 | 20.0 percentage of participants |
Secondary
Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade
An AE was any untoward medical occurrence in a participant. Treatment-related AEs are events that were assessed by the investigator as related to study medication. If the same participant in a given treatment had more than 1 occurrence in the same preferred term event category, only the worst CTCAE grade (1 = mild AE, 2 = moderate AE, 3 = severe AE, 4 = life-threatening or disabling AE, 5 = death related to AE) was reported.
Time frame: Baseline up to 28 days post last dose of study medication (maximum duration: 537 days)
Population: The safety analysis set consisted of all enrolled participants who received at least 1 dose of PF-04449913, including the lead-in dose.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-04449913 5 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 4 | 33.3 percentage of participants |
| PF-04449913 5 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 5 | 0.0 percentage of participants |
| PF-04449913 5 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 1 | 0.0 percentage of participants |
| PF-04449913 5 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 3 | 0.0 percentage of participants |
| PF-04449913 5 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 2 | 0.0 percentage of participants |
| PF-04449913 10 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 5 | 0.0 percentage of participants |
| PF-04449913 10 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 2 | 0.0 percentage of participants |
| PF-04449913 10 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 3 | 66.7 percentage of participants |
| PF-04449913 10 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 1 | 0.0 percentage of participants |
| PF-04449913 10 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 4 | 0.0 percentage of participants |
| PF-04449913 20 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 2 | 0.0 percentage of participants |
| PF-04449913 20 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 5 | 0.0 percentage of participants |
| PF-04449913 20 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 1 | 25.0 percentage of participants |
| PF-04449913 20 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 4 | 0.0 percentage of participants |
| PF-04449913 20 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 3 | 0.0 percentage of participants |
| PF-04449913 40 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 4 | 0.0 percentage of participants |
| PF-04449913 40 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 1 | 25.0 percentage of participants |
| PF-04449913 40 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 5 | 0.0 percentage of participants |
| PF-04449913 40 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 2 | 50.0 percentage of participants |
| PF-04449913 40 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 3 | 25.0 percentage of participants |
| PF-04449913 80 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 2 | 12.5 percentage of participants |
| PF-04449913 80 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 5 | 0.0 percentage of participants |
| PF-04449913 80 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 4 | 12.5 percentage of participants |
| PF-04449913 80 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 1 | 12.5 percentage of participants |
| PF-04449913 80 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 3 | 0.0 percentage of participants |
| PF-04449913 120 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 3 | 0.0 percentage of participants |
| PF-04449913 120 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 1 | 33.3 percentage of participants |
| PF-04449913 120 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 2 | 0.0 percentage of participants |
| PF-04449913 120 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 4 | 0.0 percentage of participants |
| PF-04449913 120 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 5 | 0.0 percentage of participants |
| PF-04449913 180 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 2 | 0.0 percentage of participants |
| PF-04449913 180 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 4 | 0.0 percentage of participants |
| PF-04449913 180 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 5 | 0.0 percentage of participants |
| PF-04449913 180 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 1 | 33.3 percentage of participants |
| PF-04449913 180 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 3 | 0.0 percentage of participants |
| PF-04449913 270 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 3 | 0.0 percentage of participants |
| PF-04449913 270 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 2 | 80.0 percentage of participants |
| PF-04449913 270 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 4 | 0.0 percentage of participants |
| PF-04449913 270 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 1 | 0.0 percentage of participants |
| PF-04449913 270 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 5 | 0.0 percentage of participants |
| PF-04449913 400 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 1 | 11.1 percentage of participants |
| PF-04449913 400 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 3 | 33.3 percentage of participants |
| PF-04449913 400 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 2 | 33.3 percentage of participants |
| PF-04449913 400 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 4 | 0.0 percentage of participants |
| PF-04449913 400 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 5 | 0.0 percentage of participants |
| PF-04449913 600 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 4 | 20.0 percentage of participants |
| PF-04449913 600 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 1 | 0.0 percentage of participants |
| PF-04449913 600 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 5 | 0.0 percentage of participants |
| PF-04449913 600 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 2 | 20.0 percentage of participants |
| PF-04449913 600 mg | Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade | Any AEs, Grade 3 | 40.0 percentage of participants |
Secondary
Plasma Decay Half-life (t1/2) on Lead-in
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24, 48, 96 and 120 hours post-dose during the lead-in period (Day -6)
Population: The PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest. N = number of participants with available data for this PK parameter in this period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PF-04449913 5 mg | Plasma Decay Half-life (t1/2) on Lead-in | 25.1 hours | Standard Deviation 9.6 |
| PF-04449913 10 mg | Plasma Decay Half-life (t1/2) on Lead-in | 25.1 hours | Standard Deviation 4.3 |
| PF-04449913 20 mg | Plasma Decay Half-life (t1/2) on Lead-in | 34.3 hours | Standard Deviation 14 |
| PF-04449913 40 mg | Plasma Decay Half-life (t1/2) on Lead-in | 23.3 hours | Standard Deviation 4.2 |
| PF-04449913 80 mg | Plasma Decay Half-life (t1/2) on Lead-in | 23.3 hours | Standard Deviation 8.1 |
| PF-04449913 120 mg | Plasma Decay Half-life (t1/2) on Lead-in | 26.5 hours | Standard Deviation 4 |
| PF-04449913 180 mg | Plasma Decay Half-life (t1/2) on Lead-in | 17.4 hours | Standard Deviation 3.3 |
| PF-04449913 270 mg | Plasma Decay Half-life (t1/2) on Lead-in | 23.6 hours | Standard Deviation 5.5 |
| PF-04449913 400 mg | Plasma Decay Half-life (t1/2) on Lead-in | 23.9 hours | Standard Deviation 14 |
| PF-04449913 600 mg | Plasma Decay Half-life (t1/2) on Lead-in | 19.6 hours | Standard Deviation 4.7 |
Secondary
Pre-dose Concentration (Ctrough) on Cycle 1 Day 21
Time frame: Pre-dose on Cycle 1 Day 21
Population: PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest. N = number of participants with available data for this parameter in this period. 1 participant from the 270-mg arm had dose reduction to 180 mg and is analyzed and reported under 180-mg.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04449913 5 mg | Pre-dose Concentration (Ctrough) on Cycle 1 Day 21 | 15.1 ng/mL | Geometric Coefficient of Variation 17 |
| PF-04449913 10 mg | Pre-dose Concentration (Ctrough) on Cycle 1 Day 21 | 18.9 ng/mL | Geometric Coefficient of Variation 14 |
| PF-04449913 20 mg | Pre-dose Concentration (Ctrough) on Cycle 1 Day 21 | 67.8 ng/mL | Geometric Coefficient of Variation 48 |
| PF-04449913 40 mg | Pre-dose Concentration (Ctrough) on Cycle 1 Day 21 | 170 ng/mL | Geometric Coefficient of Variation 121 |
| PF-04449913 80 mg | Pre-dose Concentration (Ctrough) on Cycle 1 Day 21 | 120 ng/mL | Geometric Coefficient of Variation 53 |
| PF-04449913 120 mg | Pre-dose Concentration (Ctrough) on Cycle 1 Day 21 | 495 ng/mL | Geometric Coefficient of Variation 56 |
| PF-04449913 180 mg | Pre-dose Concentration (Ctrough) on Cycle 1 Day 21 | 485 ng/mL | Geometric Coefficient of Variation 86 |
| PF-04449913 270 mg | Pre-dose Concentration (Ctrough) on Cycle 1 Day 21 | 428 ng/mL | — |
| PF-04449913 400 mg | Pre-dose Concentration (Ctrough) on Cycle 1 Day 21 | 1291 ng/mL | Geometric Coefficient of Variation 42 |
| PF-04449913 600 mg | Pre-dose Concentration (Ctrough) on Cycle 1 Day 21 | 1871 ng/mL | Geometric Coefficient of Variation 57 |
Secondary
Progression-Free Survival (PFS)
Time in months from start of study treatment to first documentation of objective disease progression or death due to any cause. PFS was calculated as \[first event date - date of first dose of study medication + 1\]/30.4. Disease progression was determined from oncologic assessment data (where data met the criteria for disease progression: categorized as early progressor from CP, progressor to AP or BC from CP or return to CP, progressor to AP to BC, loss of confirmed complete hematologic response, or loss of major cytogenetic response; or from adverse event data (where the outcome was Death).
Time frame: Baseline to end of study, up to 36 months
Population: The Efficacy Analysis Set consisted of all enrolled participants who received Cycle 1 Day 1 dose of PF-04449913.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-04449913 5 mg | Progression-Free Survival (PFS) | NA months |
| PF-04449913 10 mg | Progression-Free Survival (PFS) | 4.43 months |
| PF-04449913 20 mg | Progression-Free Survival (PFS) | 2.83 months |
| PF-04449913 40 mg | Progression-Free Survival (PFS) | 3.75 months |
| PF-04449913 80 mg | Progression-Free Survival (PFS) | NA months |
Secondary
Renal Clearance on Cycle 1 Day 21
Renal clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by the kidneys.
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21
Population: The PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest. N = number of participants with available data for this PK parameter in this period.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PF-04449913 5 mg | Renal Clearance on Cycle 1 Day 21 | 0.623 L/hour | — |
| PF-04449913 10 mg | Renal Clearance on Cycle 1 Day 21 | 1.36 L/hour | Geometric Coefficient of Variation 42 |
| PF-04449913 20 mg | Renal Clearance on Cycle 1 Day 21 | 0.754 L/hour | Geometric Coefficient of Variation 41 |
| PF-04449913 40 mg | Renal Clearance on Cycle 1 Day 21 | 0.385 L/hour | Geometric Coefficient of Variation 42 |
| PF-04449913 80 mg | Renal Clearance on Cycle 1 Day 21 | 1.14 L/hour | Geometric Coefficient of Variation 79 |
| PF-04449913 120 mg | Renal Clearance on Cycle 1 Day 21 | 0.403 L/hour | Geometric Coefficient of Variation 53 |
| PF-04449913 180 mg | Renal Clearance on Cycle 1 Day 21 | 1.27 L/hour | Geometric Coefficient of Variation 60 |
| PF-04449913 270 mg | Renal Clearance on Cycle 1 Day 21 | 1.21 L/hour | — |
| PF-04449913 400 mg | Renal Clearance on Cycle 1 Day 21 | 0.666 L/hour | Geometric Coefficient of Variation 27 |
| PF-04449913 600 mg | Renal Clearance on Cycle 1 Day 21 | 1.08 L/hour | Geometric Coefficient of Variation 132 |
Secondary
Time to Progression (TTP)
Time in months from start of study treatment to first documentation of objective disease progression or death due to cancer, whichever comes first. TTP was calculated as (first event date - date of first dose of study medication + 1)/30.4. Disease progression was determined from oncologic assessment data (where data met the criteria for disease progression: categorized as early progressor from chronic phase \[CP\], progressor to accelerated phase \[AP\] or blast crisis \[BC\] from CP or return to CP, progressor to AP to BC, loss of confirmed complete hematologic response, or loss of major cytogenetic response).
Time frame: Baseline to end of study, up to 36 months
Population: The Efficacy Analysis Set consisted of all enrolled participants who received Cycle 1 Day 1 dose of PF-04449913.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-04449913 5 mg | Time to Progression (TTP) | NA months |
| PF-04449913 10 mg | Time to Progression (TTP) | 10.12 months |
| PF-04449913 20 mg | Time to Progression (TTP) | 2.83 months |
| PF-04449913 40 mg | Time to Progression (TTP) | 3.75 months |
| PF-04449913 80 mg | Time to Progression (TTP) | NA months |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Cycle 1 Day 21
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24 hours post-dose on Cycle 1 Day 21
Population: PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest. N = the number of participants analyzed for Cycle 1. 1 participant from the 270-mg arm had dose reduction to 180 mg and is analyzed and reported under the 180-mg arm.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-04449913 5 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Cycle 1 Day 21 | 2.2 hours |
| PF-04449913 10 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Cycle 1 Day 21 | 1.0 hours |
| PF-04449913 20 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Cycle 1 Day 21 | 0.92 hours |
| PF-04449913 40 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Cycle 1 Day 21 | 1.0 hours |
| PF-04449913 80 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Cycle 1 Day 21 | 1.3 hours |
| PF-04449913 120 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Cycle 1 Day 21 | 2.2 hours |
| PF-04449913 180 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Cycle 1 Day 21 | 1.1 hours |
| PF-04449913 270 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Cycle 1 Day 21 | 3.1 hours |
| PF-04449913 400 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Cycle 1 Day 21 | 4.0 hours |
| PF-04449913 600 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Cycle 1 Day 21 | 3.2 hours |
Secondary
Time to Reach Maximum Observed Plasma Concentration (Tmax) on Lead-in
Time frame: Pre-dose, 0.5, 1, 2, 4, 8, 24, 48, 96 and 120 hours post-dose during the lead-in period (Day -6)
Population: The PK analysis set included all enrolled and treated (received at least 1 dose of study medication) participants who had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-04449913 5 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Lead-in | 2.0 hours |
| PF-04449913 10 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Lead-in | 2.0 hours |
| PF-04449913 20 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Lead-in | 1.0 hours |
| PF-04449913 40 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Lead-in | 1.0 hours |
| PF-04449913 80 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Lead-in | 2.0 hours |
| PF-04449913 120 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Lead-in | 2.0 hours |
| PF-04449913 180 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Lead-in | 2.0 hours |
| PF-04449913 270 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Lead-in | 2.0 hours |
| PF-04449913 400 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Lead-in | 2.0 hours |
| PF-04449913 600 mg | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Lead-in | 2.0 hours |