Phase 1 Study Of Aurora Kinase Inhibitor PF-03814735 In Patients With Advanced Solid Tumors

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00424632
• Collaborator: (none)
• Enrollment: 57
• Locations: 2
• Arm: 1
• Duration (Months): 31
• Patients Per Site: 28.5
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the maximum tolerated dose and recommended phase 2 dose of PF-03814735 administered orally as single agent in patients with advanced solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumors	Drug: PF-03814735	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Open Label, Multi-Center, Accelerated Dose-Escalation, Pharmacokinetic And Pharmacodynamic Trial Of The Oral Single Agent Aurora Kinase Inhibitor PF-03814735 In Patients With Advanced Solid Tumors For Whom No Standard Therapy Is Available
• Study Start Date: Nov 1, 2006
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jun 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single arm dose escalation	Drug: PF-03814735; 1, 5, and 25 mg gelatin capsules administered orally once a day from day 1 to day 5, or from day 1 to day 10 every 3 weeks until disease progression or unacceptable toxicity.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) Graded According to Common Terminology Criteria Adverse Events (CTCAE), Version 3 [Day 1 up to Day 21 of first cycle]

   DLT defined as any of the following during the first cycle of treatment and attributable to PF-03814735: Grade (Gr) 4 neutropenia (absolute neutrophil count [ANC] <500 cells/mm^3) for >7 days or febrile neutropenia (ANC <1000/mm^3, fever ≥38 degrees Celsius; neutropenic infection (ANC <1000/mm^3); Gr 4 thrombocytopenia (platelets <25,000 cells/mm^3); ≥Gr 3 nausea, vomiting, or diarrhea, despite optimal antiemetic, anti-diarrheal support; ≥20% decrease in left ventricular ejection fraction compared to baseline; other non-hematological toxicity; any Gr ≥3 adverse event; or failure to recover.

Secondary Outcome Measures

1. Maximum Observed Serum Concentration (Cmax) [Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose]

2. Time for Maximum Observed Serum Concentration (Tmax) [Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose]

3. Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) [Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose]

   Area under the serum concentration time-curve from zero to the last measured concentration.

4. Area Under the Serum Concentration Time Profile From Time 0 to Time Tau (τ), the Dosing Interval, Where τ = 24 Hours (AUCτ). [Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose]

5. Minimum Observed Serum Trough Concentration (Cmin) [Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose]

   Cmin defined as the lowest serum concentration observed during the dosing interval.

6. Observed Serum Accumulation Ratio (Rac) [Schedule B Day-5: pre-dose, 0.5, 1, 2, 4, 6, 10, 24, 32, 48, and 72 hours post-dose, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose]

   Rac was the ratio of Schedule B Cycle 1/Day 9 to Day -5 (Day 9 AUCτ to Day -5 AUCτ).

7. Terminal Half-life (t 1/2) [Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose]

   Terminal half-life (serum decay half-life) is the time measured for the serum concentration to decrease by one half.

8. Urine Pharmacokinetics [Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose]

   Urine PK for quantification of unchanged PF-03814375 and any identified metabolites. 24-hour urine collection at 8-hour intervals after the morning dose (Schedule [Sch] A Day 4, Sch B Day 9; last sample collected just prior to the morning dose on Sch A Day 5 or Sch B Day 10 in the expanded maximum tolerated dose (MTD) cohort only (≥ 10 participants in Sch A 80 mg and Sch B 50 mg groups). The lower limit of quantification (LLOQ) was 1 nanogram per milliliter (ng/mL). Clinical specimens with concentrations below the LLOQ were to be reported as below the limited of quantification (BLQ) 1 ng/mL.

9. Summary of Tumor Metabolism Assessed by Positron Emission Tomography With F-18-fluorodeoxyglucose (FDG-PET) [Baseline (Schedule A or Schedule B Day -7) and Schedule A Cycle 1/Day 3 or Day 4, Schedule B Cycle 1/Day 8 or 9]

   FTD-PET measured as standardized uptake volume (SUV) values corrected for lean body mass. Change from baseline categorized according to European Organization for Research and Treatment for Cancer (EORTC) criteria: Partial Metabolic Response (PMR): SUV value during treatment <75 percent (%) of baseline value; Progressive Metabolic Disease (PMD): SUV value during treatment >125% of baseline value; Stable Metabolic Disease (SMD): change in SUV value between PMR and PMD. Collected in the expanded MTD cohort only (≥ 10 participants in Sch A 80 mg and Sch B 50 mg groups).

10. Target Modulation by Phosphohistone H3 (pH3) Expression in Tumor Tissue (IHC) [Schedule A Cycle 1 or Cycle 2 /Day 4 or Day 5, Schedule B Cycle 1/Day 9 or Day 10]

    pH3 expression is a method to enable the quantification of the proliferative potential of tumor cells. Post-dose tumor tissue sampling occurred after FDG-PET. Biopsies were not to be taken from lesions which were used for PET analysis and were to be taken between 1 and 6 hours after study drug administration. Collected in the expanded MTD cohort only (≥ 10 participants in Sch A 80 mg and Sch B 50 mg groups).

11. Number of Participants With Objective Tumor Response [Every 2 cycles (each cycle=21 days) until disease progression or participant discontinuation; maximum follow-up was from baseline up to 12 cycles]

    Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.

12. Time to Progression [Baseline, every 2 cycles (each cycle=21 days) until disease progression or participant discontinuation; maximum follow-up was from baseline up to 12 cycles]

    Time to Progression defined as the time from the date of enrollment to the date progressive disease first reported. If tumor progression data included more than 1 date, the first date was to be used. TTP = (first date of tumor progression - date of enrollment + 1). Progressive disease: ≥20% increase in sum LD of target lesions from smallest sum LD recorded since treatment start or appearance of ≥1 new lesions.

13. Duration of Response [Every 2 cycles (each cycle=21 days) until disease progression or participant discontinuation; maximum follow-up was from baseline up to 12 cycles]

    Duration of responses based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.

14. Germ Line Polymorphism of Candidate Genes Targeted by PF-03814735 [Schedule A Cycle 1 or Cycle 2 /Day 4 or Day 5, Schedule B Cycle 1/Day 9 or Day 10 (each cycle=21 days)]

    Percentage of germ line polymorphism cell expression in relation to clinical response. Responses include CR: disappearance of all target lesions; PR: ≥30% decrease in sum of LD of target lesions referencing baseline sum LD; Progressive disease: ≥20% increase in sum LD of target lesions from smallest sum LD recorded since Tx start or appearance of ≥1 new lesions; Stable disease: neither sufficient shrinkage to=PR nor sufficient increase to=PD during first 6 weeks after Tx start referencing smallest sum LD since Tx start.

15. Aurora Gene Somatic Mutations/Amplification and Pathway Genes in Tumor Tissue [Schedule A Cycle 1 or Cycle 2 /Day 4 or Day 5, Schedule B Cycle 1/Day 9 or Day 10 (each cycle=21 days)]

    Percentage of aurora gene somatic mutations/amplification and pathway genes in relation to clinical response. Responses include CR: disappearance of all target lesions; PR: ≥30% decrease in sum of longest dimensions (LD) of target lesions referencing baseline sum LD; Progressive disease: ≥20% increase in sum LD of target lesions from smallest sum LD recorded since Tx start or appearance of ≥1 new lesions; Stable disease: neither sufficient shrinkage to=PR nor sufficient increase to=PD during first 6 weeks after Tx start referencing smallest sum LD since Tx start.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Metastatic solid tumor resistant to standard therapy or for which no standard therapy is available

• Adequate bone marrow, liver and kidney function

Exclusion Criteria:

• Brain metastases that are symptomatic and/or require treatment with steroids and/or anticonvulsants, or brain metastases that have been treated within 3 months prior to study start

• Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure, cerebrovascular accident in the previous 6 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Nashville	Tennessee	United States	37203
2	Pfizer Investigational Site	Leuven		Belgium	3000

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00424632
• Other Study ID Numbers: A9491001
• First Posted: Jan 19, 2007
• Last Update Posted: Jun 25, 2012
• Last Verified: Jun 1, 2012

• Additional relevant MeSH terms: Neoplasms

Study Results

Participant Flow

Pre-assignment Detail	59 participants enrolled and 57 sequentially assigned to treatment in Schedule A or B of study treatment. Schedule A: starting dose was 5 milligrams per day (mg/day) and dose was escalated up to 100 mg/day. Schedule B: starting dose determined based on occurrence of dose limiting toxicities and maximum tolerated dose in Schedule A.

Arm/Group Title	PF-03814735 5 mg (Schedule A)	PF-03814735 10 mg (Schedule A)	PF-03814735 20 mg (Schedule A)	PF-03814735 40 mg (Schedule A)	PF-03814735 60 mg (Schedule A)	PF-03814735 80 mg (Schedule A)	PF-03814735 100 mg (Schedule A)	PF-03814735 40 mg (Schedule B)	PF-03814735 50 mg (Schedule B)	PF-03814735 60 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Period Title: Overall Study
STARTED	1	1	1	4	3	15	7	3	16	6
COMPLETED	0	0	0	0	0	0	0	0	0	0
NOT COMPLETED	1	1	1	4	3	15	7	3	16	6

Baseline Characteristics

Arm/Group Title	PF-03814735 (Schedule A)	PF-03814735 (Schedule B)	Total
Arm/Group Description	Participants received daily dosing of PF-03814735 of 5, 10, 20, 40, 60, 80, or 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40, 50, or 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Total of all reporting groups
Overall Participants	32	25	57
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.6 (9.0)	58.2 (10.2)	61.2 (9.8)
Sex: Female, Male (Count of Participants)
Female	18 56.3%	13 52%	31 54.4%
Male	14 43.8%	12 48%	26 45.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) Graded According to Common Terminology Criteria Adverse Events (CTCAE), Version 3
Description	DLT defined as any of the following during the first cycle of treatment and attributable to PF-03814735: Grade (Gr) 4 neutropenia (absolute neutrophil count [ANC] <500 cells/mm^3) for >7 days or febrile neutropenia (ANC <1000/mm^3, fever ≥38 degrees Celsius; neutropenic infection (ANC <1000/mm^3); Gr 4 thrombocytopenia (platelets <25,000 cells/mm^3); ≥Gr 3 nausea, vomiting, or diarrhea, despite optimal antiemetic, anti-diarrheal support; ≥20% decrease in left ventricular ejection fraction compared to baseline; other non-hematological toxicity; any Gr ≥3 adverse event; or failure to recover.
Time Frame	Day 1 up to Day 21 of first cycle

Outcome Measure Data

Analysis Population Description

Safety population: Same as the As-treated population, defined as all patients enrolled in the study that received at least 1 dose of the study medication.

Arm/Group Title	PF-03814735 5 mg (Schedule A)	PF-03814735 10 mg (Schedule A)	PF-03814735 20 mg (Schedule A)	PF-03814735 40 mg (Schedule A)	PF-03814735 60 mg (Schedule A)	PF-03814735 80 mg (Schedule A)	PF-03814735 100 mg (Schedule A)	PF-03814735 40 mg (Schedule B)	PF-03814735 50 mg (Schedule B)	PF-03814735 60 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Measure Participants	1	1	1	4	3	15	7	3	16	6
Number [participants]	0 0%	0 0%	0 0%	0 NaN	0 NaN	1 NaN	2 NaN	0 NaN	1 NaN	2 NaN

2. Secondary Outcome

Title	Maximum Observed Serum Concentration (Cmax)
Time Frame	Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) parameter analysis set: Enrolled participants who received at least 1 dose of study treatment who had at least 1 of the PK parameters of interest estimated in at least 1 treatment period.

Arm/Group Title	PF-03814735 5 mg (Schedule A)	PF-03814735 10 mg (Schedule A)	PF-03814735 20 mg (Schedule A)	PF-03814735 40 mg (Schedule A)	PF-03814735 60 mg (Schedule A)	PF-03814735 80 mg (Schedule A)	PF-03814735 100 mg (Schedule A)	PF-03814735 25 mg (Schedule B)	PF-03814735 40 mg (Schedule B)	PF-03814735 50 mg (Schedule B)	PF-03814735 60 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participant was randomized to receive daily dosing of PF-03814735 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis. However, participant had reduced dose of 25 mg beginning on Cycle 1 Day 1 of treatment.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Measure Participants	1	1	1	4	3	15	7	1	3	13	6
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	0.1920 (NA)	0.6470 (NA)	0.9010 (NA)	1.965 (35)	3.724 (30)	3.773 (43)	4.106 (46)	1.470 (NA)	1.957 (36)	2.786 (50)	2.087 (24)

3. Secondary Outcome

Title	Time for Maximum Observed Serum Concentration (Tmax)
Time Frame	Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis set

Arm/Group Title	PF-03814735 5 mg (Schedule A)	PF-03814735 10 mg (Schedule A)	PF-03814735 20 mg (Schedule A)	PF-03814735 40 mg (Schedule A)	PF-03814735 60 mg (Schedule A)	PF-03814735 80 mg (Schedule A)	PF-03814735 100 mg (Schedule A)	PF-03814735 25 mg (Schedule B)	PF-03814735 40 mg (Schedule B)	PF-03814735 50 mg (Schedule B)	PF-03814735 60 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participant was randomized to receive daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis. However, participant had reduced dose of 25 mg beginning on Cycle 1 Day 1 of treatment.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Measure Participants	1	1	1	4	3	15	7	1	3	13	6
Median (Full Range) [hours]	2.00 (NA)	1.00 (NA)	24.0 (NA)	1.50 (144)	2.00 (79)	2.00 (63)	2.00 (56)	2.00 (NA)	1.00 (79)	2.00 (59)	1.50 (61)

4. Secondary Outcome

Title	Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)
Description	Area under the serum concentration time-curve from zero to the last measured concentration.
Time Frame	Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

Data was not summarized as the development of the compound was discontinued.

Arm/Group Title	PF-03814735 5 mg (Schedule A)	PF-03814735 10 mg (Schedule A)	PF-03814735 20 mg (Schedule A)	PF-03814735 40 mg (Schedule A)	PF-03814735 60 mg (Schedule A)	PF-03814735 80 mg (Schedule A)	PF-03814735 100 mg (Schedule A)	PF-03814735 25 mg (Schedule B)	PF-03814735 40 mg (Schedule B)	PF-03814735 50 mg (Schedule B)	PF-03814735 60 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participant was randomized to receive daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis. However, participant had reduced dose of 25 mg beginning on Cycle 1 Day 1 of treatment.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Measure Participants	0	0	0	0	0	0	0	0	0	0	0

5. Secondary Outcome

Title	Area Under the Serum Concentration Time Profile From Time 0 to Time Tau (τ), the Dosing Interval, Where τ = 24 Hours (AUCτ).
Time Frame	Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis set

Arm/Group Title	PF-03814735 5 mg (Schedule A)	PF-03814735 10 mg (Schedule A)	PF-03814735 20 mg (Schedule A)	PF-03814735 40 mg (Schedule A)	PF-03814735 60 mg (Schedule A)	PF-03814735 80 mg (Schedule A)	PF-03814735 100 mg (Schedule A)	PF-03814735 25 mg (Schedule B)	PF-03814735 40 mg (Schedule B)	PF-03814735 50 mg (Schedule B)	PF-03814735 60 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participant was randomized to receive daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis. However, participant had reduced dose of 25 mg beginning on Cycle 1 Day 1 of treatment.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Measure Participants	1	1	1	4	3	15	7	1	3	13	6
Geometric Mean (Geometric Coefficient of Variation) [mcg*hr/mL]	2.957 (NA)	10.09 (NA)	17.68 (NA)	22.99 (17)	47.95 (62)	49.33 (58)	57.96 (45)	22.69 (NA)	22.08 (90)	37.15 (66)	24.12 (24)

6. Secondary Outcome

Title	Minimum Observed Serum Trough Concentration (Cmin)
Description	Cmin defined as the lowest serum concentration observed during the dosing interval.
Time Frame	Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis set

Arm/Group Title	PF-03814735 5 mg (Schedule A)	PF-03814735 10 mg (Schedule A)	PF-03814735 20 mg (Schedule A)	PF-03814735 40 mg (Schedule A)	PF-03814735 60 mg (Schedule A)	PF-03814735 80 mg (Schedule A)	PF-03814735 100 mg (Schedule A)	PF-03814735 25 mg (Schedule B)	PF-03814735 40 mg (Schedule B)	PF-03814735 50 mg (Schedule B)	PF-03814735 60 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participant was randomized to receive daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis. However, participant had reduced dose of 25 mg beginning on Cycle 1 Day 1 of treatment.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Measure Participants	1	1	1	4	3	15	7	1	3	13	6
Geometric Mean (Geometric Coefficient of Variation) [mcg/mL]	0.05440 (NA)	0.2330 (NA)	0.3110 (NA)	0.4521 (27)	1.019 (105)	1.061 (86)	1.410 (58)	0.4950 (NA)	0.3901 (271)	0.6636 (178)	0.4217 (61)

7. Secondary Outcome

Title	Observed Serum Accumulation Ratio (Rac)
Description	Rac was the ratio of Schedule B Cycle 1/Day 9 to Day -5 (Day 9 AUCτ to Day -5 AUCτ).
Time Frame	Schedule B Day-5: pre-dose, 0.5, 1, 2, 4, 6, 10, 24, 32, 48, and 72 hours post-dose, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis set. N=number of participants in the indicated population contributing to the mean.

Arm/Group Title	PF-03814735 40 mg (Schedule B)	PF-03814735 50 mg (Schedule B)	PF-03814735 60 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Measure Participants	3	13	6
Geometric Mean (Geometric Coefficient of Variation) [ratio]	1.054 (28)	1.503 (44)	1.247 (27)

8. Secondary Outcome

Title	Terminal Half-life (t 1/2)
Description	Terminal half-life (serum decay half-life) is the time measured for the serum concentration to decrease by one half.
Time Frame	Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

Half-life (t ½) was not reported for multiple-dose data since the 24-hour sampling period was not long enough to adequately characterize t ½.

Arm/Group Title	PF-03814735 5 mg (Schedule A)	PF-03814735 10 mg (Schedule A)	PF-03814735 20 mg (Schedule A)	PF-03814735 40 mg (Schedule A)	PF-03814735 60 mg (Schedule A)	PF-03814735 80 mg (Schedule A)	PF-03814735 100 mg (Schedule A)	PF-03814735 25 mg (Schedule B)	PF-03814735 40 mg (Schedule B)	PF-03814735 50 mg (Schedule B)	PF-03814735 60 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participant was randomized to receive daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis. However, participant had reduced dose of 25 mg beginning on Cycle 1 Day 1 of treatment.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Measure Participants	0	0	0	0	0	0	0	0	0	0	0

9. Secondary Outcome

Title	Urine Pharmacokinetics
Description	Urine PK for quantification of unchanged PF-03814375 and any identified metabolites. 24-hour urine collection at 8-hour intervals after the morning dose (Schedule [Sch] A Day 4, Sch B Day 9; last sample collected just prior to the morning dose on Sch A Day 5 or Sch B Day 10 in the expanded maximum tolerated dose (MTD) cohort only (≥ 10 participants in Sch A 80 mg and Sch B 50 mg groups). The lower limit of quantification (LLOQ) was 1 nanogram per milliliter (ng/mL). Clinical specimens with concentrations below the LLOQ were to be reported as below the limited of quantification (BLQ) 1 ng/mL.
Time Frame	Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

Outcome Measure Data

Analysis Population Description

Data was not summarized as the development of the compound was discontinued.

Arm/Group Title	PF-03814735 80 mg (Schedule A)	PF-03814735 50 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Measure Participants	0	0

10. Secondary Outcome

Title	Summary of Tumor Metabolism Assessed by Positron Emission Tomography With F-18-fluorodeoxyglucose (FDG-PET)
Description	FTD-PET measured as standardized uptake volume (SUV) values corrected for lean body mass. Change from baseline categorized according to European Organization for Research and Treatment for Cancer (EORTC) criteria: Partial Metabolic Response (PMR): SUV value during treatment <75 percent (%) of baseline value; Progressive Metabolic Disease (PMD): SUV value during treatment >125% of baseline value; Stable Metabolic Disease (SMD): change in SUV value between PMR and PMD. Collected in the expanded MTD cohort only (≥ 10 participants in Sch A 80 mg and Sch B 50 mg groups).
Time Frame	Baseline (Schedule A or Schedule B Day -7) and Schedule A Cycle 1/Day 3 or Day 4, Schedule B Cycle 1/Day 8 or 9

Outcome Measure Data

Analysis Population Description

Data was not summarized as the development of the compound was discontinued.

Arm/Group Title	PF-03814735 80 mg (Schedule A)	PF-03814735 50 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Measure Participants	0	0

11. Secondary Outcome

Title	Target Modulation by Phosphohistone H3 (pH3) Expression in Tumor Tissue (IHC)
Description	pH3 expression is a method to enable the quantification of the proliferative potential of tumor cells. Post-dose tumor tissue sampling occurred after FDG-PET. Biopsies were not to be taken from lesions which were used for PET analysis and were to be taken between 1 and 6 hours after study drug administration. Collected in the expanded MTD cohort only (≥ 10 participants in Sch A 80 mg and Sch B 50 mg groups).
Time Frame	Schedule A Cycle 1 or Cycle 2 /Day 4 or Day 5, Schedule B Cycle 1/Day 9 or Day 10

Outcome Measure Data

Analysis Population Description

Data was not summarized as the development of the compound was discontinued.

Arm/Group Title	PF-03814735 80 mg (Schedule A)	PF-03814735 50 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Measure Participants	0	0

12. Secondary Outcome

Title	Number of Participants With Objective Tumor Response
Description	Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
Time Frame	Every 2 cycles (each cycle=21 days) until disease progression or participant discontinuation; maximum follow-up was from baseline up to 12 cycles

Outcome Measure Data

Analysis Population Description

Data was not summarized as the development of the compound was discontinued.

Arm/Group Title	PF-03814735 5 mg (Schedule A)	PF-03814735 10 mg (Schedule A)	PF-03814735 20 mg (Schedule A)	PF-03814735 40 mg (Schedule A)	PF-03814735 60 mg (Schedule A)	PF-03814735 80 mg (Schedule A)	PF-03814735 100 mg (Schedule A)	PF-03814735 40 mg (Schedule B)	PF-03814735 50 mg (Schedule B)	PF-03814735 60 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Measure Participants	0	0	0	0	0	0	0	0	0	0

13. Secondary Outcome

Title	Time to Progression
Description	Time to Progression defined as the time from the date of enrollment to the date progressive disease first reported. If tumor progression data included more than 1 date, the first date was to be used. TTP = (first date of tumor progression - date of enrollment + 1). Progressive disease: ≥20% increase in sum LD of target lesions from smallest sum LD recorded since treatment start or appearance of ≥1 new lesions.
Time Frame	Baseline, every 2 cycles (each cycle=21 days) until disease progression or participant discontinuation; maximum follow-up was from baseline up to 12 cycles

Outcome Measure Data

Analysis Population Description

Data was not summarized as the development of the compound was discontinued.

Arm/Group Title	PF-03814735 5 mg (Schedule A)	PF-03814735 10 mg (Schedule A)	PF-03814735 20 mg (Schedule A)	PF-03814735 40 mg (Schedule A)	PF-03814735 60 mg (Schedule A)	PF-03814735 80 mg (Schedule A)	PF-03814735 100 mg (Schedule A)	PF-03814735 40 mg (Schedule B)	PF-03814735 50 mg (Schedule B)	PF-03814735 60 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Measure Participants	0	0	0	0	0	0	0	0	0	0

14. Secondary Outcome

Title	Duration of Response
Description	Duration of responses based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
Time Frame	Every 2 cycles (each cycle=21 days) until disease progression or participant discontinuation; maximum follow-up was from baseline up to 12 cycles

Outcome Measure Data

Analysis Population Description

Data was not summarized as the development of the compound was discontinued.

Arm/Group Title	PF-03814735 5 mg (Schedule A)	PF-03814735 10 mg (Schedule A)	PF-03814735 20 mg (Schedule A)	PF-03814735 40 mg (Schedule A)	PF-03814735 60 mg (Schedule A)	PF-03814735 80 mg (Schedule A)	PF-03814735 100 mg (Schedule A)	PF-03814735 40 mg (Schedule B)	PF-03814735 50 mg (Schedule B)	PF-03814735 60 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Measure Participants	0	0	0	0	0	0	0	0	0	0

15. Secondary Outcome

Title	Germ Line Polymorphism of Candidate Genes Targeted by PF-03814735
Description	Percentage of germ line polymorphism cell expression in relation to clinical response. Responses include CR: disappearance of all target lesions; PR: ≥30% decrease in sum of LD of target lesions referencing baseline sum LD; Progressive disease: ≥20% increase in sum LD of target lesions from smallest sum LD recorded since Tx start or appearance of ≥1 new lesions; Stable disease: neither sufficient shrinkage to=PR nor sufficient increase to=PD during first 6 weeks after Tx start referencing smallest sum LD since Tx start.
Time Frame	Schedule A Cycle 1 or Cycle 2 /Day 4 or Day 5, Schedule B Cycle 1/Day 9 or Day 10 (each cycle=21 days)

Outcome Measure Data

Analysis Population Description

Data was not summarized as the development of the compound was discontinued.

Arm/Group Title	PF-03814735 80 mg (Schedule A)	PF-03814735 50 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Measure Participants	0	0

16. Secondary Outcome

Title	Aurora Gene Somatic Mutations/Amplification and Pathway Genes in Tumor Tissue
Description	Percentage of aurora gene somatic mutations/amplification and pathway genes in relation to clinical response. Responses include CR: disappearance of all target lesions; PR: ≥30% decrease in sum of longest dimensions (LD) of target lesions referencing baseline sum LD; Progressive disease: ≥20% increase in sum LD of target lesions from smallest sum LD recorded since Tx start or appearance of ≥1 new lesions; Stable disease: neither sufficient shrinkage to=PR nor sufficient increase to=PD during first 6 weeks after Tx start referencing smallest sum LD since Tx start.
Time Frame	Schedule A Cycle 1 or Cycle 2 /Day 4 or Day 5, Schedule B Cycle 1/Day 9 or Day 10 (each cycle=21 days)

Outcome Measure Data

Analysis Population Description

Data was not summarized as the development of the compound was discontinued.

Arm/Group Title	PF-03814735 80 mg (Schedule A)	PF-03814735 50 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
Measure Participants	0	0

Adverse Events

Time Frame	Treatment emergent events are reported from the first dose of study treatment up to 28 days after last dose of study treatment.
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
Arm/Group Title	PF-03814735 5 mg (Schedule A)		PF-03814735 10 mg (Schedule A)		PF-03814735 20 mg (Schedule A)		PF-03814735 40 mg (Schedule A)		PF-03814735 60 mg (Schedule A)		PF-03814735 80 mg (Schedule A)		PF-03814735 100 mg (Schedule A)		PF-03814735 40 mg (Schedule B)		PF-03814735 50 mg (Schedule B)		PF-03814735 60 mg (Schedule B)
Arm/Group Description	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.		Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.		Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.		Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.		Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.		Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.		Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.		Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.		Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.		Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
All Cause Mortality
	PF-03814735 5 mg (Schedule A)		PF-03814735 10 mg (Schedule A)		PF-03814735 20 mg (Schedule A)		PF-03814735 40 mg (Schedule A)		PF-03814735 60 mg (Schedule A)		PF-03814735 80 mg (Schedule A)		PF-03814735 100 mg (Schedule A)		PF-03814735 40 mg (Schedule B)		PF-03814735 50 mg (Schedule B)		PF-03814735 60 mg (Schedule B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	PF-03814735 5 mg (Schedule A)		PF-03814735 10 mg (Schedule A)		PF-03814735 20 mg (Schedule A)		PF-03814735 40 mg (Schedule A)		PF-03814735 60 mg (Schedule A)		PF-03814735 80 mg (Schedule A)		PF-03814735 100 mg (Schedule A)		PF-03814735 40 mg (Schedule B)		PF-03814735 50 mg (Schedule B)		PF-03814735 60 mg (Schedule B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/1 (0%)		1/1 (100%)		1/4 (25%)		1/3 (33.3%)		4/15 (26.7%)		2/7 (28.6%)		0/3 (0%)		5/16 (31.3%)		0/6 (0%)
Blood and lymphatic system disorders
Anaemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Febrile neutropenia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		2/7 (28.6%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Neutropenia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)
Cardiac disorders
Supraventricular tachycardia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Gastrointestinal disorders
Ascites	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Proctalgia	0/1 (0%)		0/1 (0%)		1/1 (100%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
General disorders
Disease progression	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		1/3 (33.3%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Pyrexia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Hepatobiliary disorders
Cholecystitis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Infections and infestations
Sepsis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Urinary tract infection	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Metabolism and nutrition disorders
Dehydration	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/4 (25%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Hypercalcaemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Hypokalaemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/4 (25%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Hyponatraemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	PF-03814735 5 mg (Schedule A)		PF-03814735 10 mg (Schedule A)		PF-03814735 20 mg (Schedule A)		PF-03814735 40 mg (Schedule A)		PF-03814735 60 mg (Schedule A)		PF-03814735 80 mg (Schedule A)		PF-03814735 100 mg (Schedule A)		PF-03814735 40 mg (Schedule B)		PF-03814735 50 mg (Schedule B)		PF-03814735 60 mg (Schedule B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		1/1 (100%)		1/1 (100%)		4/4 (100%)		3/3 (100%)		15/15 (100%)		7/7 (100%)		3/3 (100%)		15/16 (93.8%)		6/6 (100%)
Blood and lymphatic system disorders
Anaemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		1/3 (33.3%)		6/15 (40%)		1/7 (14.3%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Leukopenia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		1/7 (14.3%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Neutropenia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		3/15 (20%)		2/7 (28.6%)		1/3 (33.3%)		3/16 (18.8%)		1/6 (16.7%)
Thrombocytopenia	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/4 (25%)		0/3 (0%)		4/15 (26.7%)		1/7 (14.3%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Cardiac disorders
Left ventricular dysfunction	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		2/6 (33.3%)
Myocardial infarction	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Palpitations	1/1 (100%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Eye disorders
Conjunctivitis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)
Glare	1/1 (100%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Vision blurred	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Gastrointestinal disorders
Abdominal discomfort	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		3/15 (20%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Abdominal distension	1/1 (100%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Abdominal pain	0/1 (0%)		0/1 (0%)		1/1 (100%)		1/4 (25%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Abdominal pain lower	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		1/7 (14.3%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Abdominal pain upper	1/1 (100%)		0/1 (0%)		0/1 (0%)		2/4 (50%)		0/3 (0%)		3/15 (20%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Anal haemorrhage	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Anorectal discomfort	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Ascites	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		1/3 (33.3%)		0/16 (0%)		0/6 (0%)
Constipation	0/1 (0%)		0/1 (0%)		0/1 (0%)		2/4 (50%)		1/3 (33.3%)		6/15 (40%)		1/7 (14.3%)		2/3 (66.7%)		2/16 (12.5%)		0/6 (0%)
Diarrhoea	0/1 (0%)		0/1 (0%)		1/1 (100%)		3/4 (75%)		2/3 (66.7%)		7/15 (46.7%)		4/7 (57.1%)		2/3 (66.7%)		7/16 (43.8%)		3/6 (50%)
Dry mouth	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		2/15 (13.3%)		1/7 (14.3%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Dysphagia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		1/3 (33.3%)		0/16 (0%)		0/6 (0%)
Haemorrhoids	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		1/3 (33.3%)		0/16 (0%)		0/6 (0%)
Nausea	0/1 (0%)		0/1 (0%)		1/1 (100%)		1/4 (25%)		0/3 (0%)		7/15 (46.7%)		4/7 (57.1%)		1/3 (33.3%)		5/16 (31.3%)		4/6 (66.7%)
Pancreatitis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Rectal haemorrhage	0/1 (0%)		0/1 (0%)		1/1 (100%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Rectal tenesmus	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Stomatitis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		2/7 (28.6%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Toothache	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)
Vomiting	0/1 (0%)		0/1 (0%)		1/1 (100%)		3/4 (75%)		1/3 (33.3%)		5/15 (33.3%)		2/7 (28.6%)		0/3 (0%)		4/16 (25%)		2/6 (33.3%)
General disorders
Asthenia	0/1 (0%)		0/1 (0%)		1/1 (100%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Chest pain	0/1 (0%)		1/1 (100%)		0/1 (0%)		0/4 (0%)		1/3 (33.3%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)
Death	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Disease progression	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Face oedema	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Fatigue	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		2/3 (66.7%)		9/15 (60%)		3/7 (42.9%)		1/3 (33.3%)		5/16 (31.3%)		4/6 (66.7%)
Gait disturbance	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		1/3 (33.3%)		0/16 (0%)		0/6 (0%)
General physical health deterioration	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/4 (25%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Influenza like illness	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Mucosal inflammation	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		1/3 (33.3%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)
Oedema	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Oedema peripheral	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		1/3 (33.3%)		0/15 (0%)		1/7 (14.3%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Pyrexia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		1/3 (33.3%)		2/15 (13.3%)		0/7 (0%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)
Secretion discharge	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)
Swelling	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)
Hepatobiliary disorders
Hepatic function abnormal	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Hepatic pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Hyperbilirubinaemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Immune system disorders
Seasonal allergy	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/4 (25%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Infections and infestations
Escherichia bacteraemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Gastroenteritis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		1/7 (14.3%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Hordeolum	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Nasopharyngitis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		1/7 (14.3%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Pneumonia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		1/7 (14.3%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Sinusitis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Streptococcal infection	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		1/7 (14.3%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Urinary tract infection	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)
Viral infection	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Injury, poisoning and procedural complications
Contusion	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		1/7 (14.3%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Fall	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		1/3 (33.3%)		1/16 (6.3%)		0/6 (0%)
Wound	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)
Investigations
Aspartate aminotransferase increased	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)
Blood amylase increased	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Blood creatinine increased	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		1/3 (33.3%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Blood potassium increased	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Cardiac murmur	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		1/7 (14.3%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Ejection fraction decreased	0/1 (0%)		0/1 (0%)		1/1 (100%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Lipase increased	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Troponin increased	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Weight decreased	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/4 (25%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/1 (0%)		1/1 (100%)		0/1 (0%)		2/4 (50%)		1/3 (33.3%)		6/15 (40%)		2/7 (28.6%)		1/3 (33.3%)		2/16 (12.5%)		1/6 (16.7%)
Hypercalcaemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Hyperkalaemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Hypomagnesaemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		1/7 (14.3%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Hyponatraemia	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/4 (25%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Polydipsia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		2/15 (13.3%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/4 (25%)		0/3 (0%)		2/15 (13.3%)		1/7 (14.3%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)
Back pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		2/16 (12.5%)		1/6 (16.7%)
Bone pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Flank pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		1/3 (33.3%)		0/16 (0%)		0/6 (0%)
Muscular weakness	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Musculoskeletal chest pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Musculoskeletal pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		2/15 (13.3%)		0/7 (0%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)
Myalgia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		2/16 (12.5%)		1/6 (16.7%)
Neck mass	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/4 (25%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Neck pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		1/3 (33.3%)		0/16 (0%)		0/6 (0%)
Pain in extremity	0/1 (0%)		0/1 (0%)		1/1 (100%)		0/4 (0%)		0/3 (0%)		2/15 (13.3%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)
Nervous system disorders
Ageusia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Dizziness	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		2/15 (13.3%)		0/7 (0%)		2/3 (66.7%)		2/16 (12.5%)		0/6 (0%)
Dysarthria	0/1 (0%)		1/1 (100%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Dysgeusia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		1/7 (14.3%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Headache	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/4 (25%)		0/3 (0%)		1/15 (6.7%)		1/7 (14.3%)		1/3 (33.3%)		2/16 (12.5%)		1/6 (16.7%)
Memory impairment	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Neuropathy peripheral	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		1/3 (33.3%)		2/16 (12.5%)		1/6 (16.7%)
Peripheral motor neuropathy	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Peripheral sensory neuropathy	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		1/7 (14.3%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Somnolence	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		1/3 (33.3%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Syncope	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		1/7 (14.3%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Psychiatric disorders
Anxiety	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/4 (25%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Anxiety disorder	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/4 (25%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Confusional state	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		1/3 (33.3%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Depression	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		2/15 (13.3%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)
Insomnia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		1/3 (33.3%)		2/16 (12.5%)		0/6 (0%)
Mood altered	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)
Renal and urinary disorders
Haematuria	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Urinary incontinence	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Reproductive system and breast disorders
Scrotal pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Vaginal discharge	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)
Respiratory, thoracic and mediastinal disorders
Cough	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/4 (25%)		0/3 (0%)		4/15 (26.7%)		2/7 (28.6%)		0/3 (0%)		2/16 (12.5%)		1/6 (16.7%)
Dysphonia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		1/7 (14.3%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Dyspnoea	0/1 (0%)		0/1 (0%)		1/1 (100%)		1/4 (25%)		1/3 (33.3%)		1/15 (6.7%)		1/7 (14.3%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)
Epistaxis	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/4 (25%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Hiccups	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Oropharyngeal pain	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		1/6 (16.7%)
Productive cough	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		1/6 (16.7%)
Pulmonary embolism	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Rales	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Sinus congestion	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		1/3 (33.3%)		0/15 (0%)		1/7 (14.3%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Throat tightness	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		1/3 (33.3%)		0/16 (0%)		0/6 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		2/15 (13.3%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Hyperhidrosis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Hypoaesthesia facial	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Night sweats	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Rash	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		1/3 (33.3%)		2/15 (13.3%)		1/7 (14.3%)		0/3 (0%)		2/16 (12.5%)		0/6 (0%)
Skin lesion	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		1/7 (14.3%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Surgical and medical procedures
Sinus operation	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Vascular disorders
Flushing	0/1 (0%)		1/1 (100%)		1/1 (100%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Hot flush	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/4 (25%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Hypertension	0/1 (0%)		0/1 (0%)		0/1 (0%)		1/4 (25%)		0/3 (0%)		0/15 (0%)		1/7 (14.3%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Hypotension	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		0/15 (0%)		0/7 (0%)		0/3 (0%)		1/16 (6.3%)		0/6 (0%)
Jugular vein thrombosis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Subclavian vein thrombosis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)
Vena cava thrombosis	0/1 (0%)		0/1 (0%)		0/1 (0%)		0/4 (0%)		0/3 (0%)		1/15 (6.7%)		0/7 (0%)		0/3 (0%)		0/16 (0%)		0/6 (0%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.