A Dose Finding Study Of A New Medication, PF-00337210 That Will Possibly Decrease Blood Supply To Tumors

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01105533
• Collaborator: University of Wisconsin, Madison (Other)
• Enrollment: 46
• Locations: 3
• Arms: 10
• Duration (Months): 64
• Patients Per Site: 15.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will test a new cancer medication to determine if this medication will block blood supply to a tumor and decrease growth of a tumor. This study will also define the safety profile and define the safest dose of this new medication for people who have cancer.

Condition or Disease	Intervention/Treatment	Phase
Neoplasm	Drug: PF-00337210; Drug: PF-00337210; Drug: PF-00337210; Drug: PF-00337210; Drug: PF-00337210; Drug: PF-00337210; Drug: PF-00337210; Drug: PF-00337210; Drug: PF-00337210; Drug: PF-00337210	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 46 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I, Open-Label, Multi-Center, Accelerated Dose Escalation Study Of The Anti-Angiogenesis Agent PF-00337210 In Patients With Advanced Solid Tumors
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Oct 1, 2010
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1	Drug: PF-00337210; 0.67mg Capsule Once Daily (Accelerated Dose Escalation) Continuous
Experimental: Cohort 2	Drug: PF-00337210; 1mg Capsule Once Daily (Dose Escalation) Continuous
Experimental: Cohort 3	Drug: PF-00337210; 2mg Capsule Once Daily (Dose Escalation) Continuous
Experimental: Cohort 4	Drug: PF-00337210; 4mg Capsule Once Daily (Dose Escalation) Continuous
Experimental: Cohort 5	Drug: PF-00337210; 6mg Capsule Once Daily (Dose Escalation) Continuous
Experimental: Cohort 6	Drug: PF-00337210; 9mg Capsule Once Daily (Dose Escalation) Continuous
Experimental: Cohort 7	Drug: PF-00337210; 8mg Capsule Once Daily (Dose Escalation) Continuous
Experimental: Cohort 8	Drug: PF-00337210; 4mg Capsule Twice Daily (Dose Escalation) Continuous
Experimental: Cohort 9	Drug: PF-00337210; 6mg Capsule Twice Daily (Dose Escalation) Continuous
Experimental: Cohort 10	Drug: PF-00337210; 6mg Capsule Twice Daily (Dose Expansion) Continuous

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose-limiting Toxicities (DLTs) [Baseline up to Day 28]

   DLTs included events occurring in Cycle 1: blood pressure of 180/110 millimeters of mercury (mmHg) or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or greater than (>) 160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia for greater than or equal to (>=) 7 days or >=Grade 3 neutropenia associated with fever (1 reading of oral temperature >38.5 degree Celsius [degree C] or 3 readings of oral temperature >38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of >1/2 teaspoon of bright red blood per day; proteinuria of >=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; >=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.

2. Maximum Tolerated Dose (MTD) [Day 28]

   MTD: dose level at which no more than 1 of 6 participants experienced DLT during Cycle 1. DLTs: blood pressure of 180/110 mmHg or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or >160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia >=7 days or >= Grade 3 neutropenia associated with fever (1 reading of oral temperature >38.5 degree C or 3 readings of oral temperature >38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of >1/2 teaspoon of bright red blood per day; proteinuria of >=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; >=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.

3. Maximum Administered Dose (MAD) [Day 28]

   MAD: dose level at which 2 or more out of 6 participants experienced DLT during Cycle 1. DLTs: blood pressure of 180/110 mmHg or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or >160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia >=7 days or >= Grade 3 neutropenia associated with fever (1 reading of oral temperature >38.5 degree C or 3 readings of oral temperature >38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of >1/2 teaspoon of bright red blood per day; proteinuria of >=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; >=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.

4. Recommended Phase-2 Dose (RP2D) [Day 28]

   RP2D was determined based on the safety profile and pharmacodynamic findings. The twice daily dosing was preferred over once daily dosing for RP2D, as per investigator's discretion, due to more consistent changes in pharmacodynamic markers and greater clinical benefit observed in twice daily dosing.

Secondary Outcome Measures

1. Maximum Observed Plasma Concentration (Cmax) [Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hours(hrs) post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57]

2. Plasma Decay Half-Life (t1/2) [Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57]

   Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.

3. Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] [Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57]

   AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).

4. Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)] [Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57]

   AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).

5. Apparent Volume of Distribution (Vss) [Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57]

   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 is influenced by the fraction absorbed.

6. Systemic Clearance (CL) [Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57]

   CL is a quantitative measure of the rate at which a drug substance is removed from the body.

7. Number of Participants With Objective Response of Complete Response or Partial Response [Baseline, every 8 weeks up to Cycle 25 (Week 100)]

   Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target and non-target lesions and no appearance of new lesions. Confirmed PR defined as at least 30 percent decrease in sum of the longest dimensions (LD) of the target lesions, taking as a reference the baseline sum LD, without progression of non-target lesions and no appearance of new lesions. Confirmed responses are those that persist on repeat imaging study >=4 weeks after initial documentation of response.

8. Change From Baseline in Biomarkers at Day 1 of Each Cycle up to Cycle 25 [Baseline, Day 1 of Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25]

   Biomarkers included soluble plasma proteins associated with angiogenesis (vascular endothelial growth factor [VEGF], soluble vascular endothelial growth factor-2 receptor [sVEGFR2], soluble vascular endothelial growth factor-3 receptor [sVEGFR3], soluble beta type platelet-derived growth factor [sPDGFR beta]) and tumor proliferation (soluble stem-cell factor receptor [sKIT])

Other Outcome Measures

1. Effect of Food on Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)] [Pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 29 (fasted state), Day 30 (fed state) for once daily groups, pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 29 Day 29 (fasted state), Day 30 (fed state) for twice daily groups]

   AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed advanced solid tumors un-responsive to currently available therapies or for which there is no standard therapy.

• At least 1 measurable disease site as defined by Response Evaluation Criterion in Solid Tumors [RECIST].

• Adequate bone marrow, liver function and renal function as defined by protocol.

• Blood pressure Requirements During dose escalation - no evidence of pre-existing hypertension and no antihypertensive medications at baseline.

During dose expansion - patient's whose hypertension is controlled by antihypertensive therapy.

Exclusion Criteria:

• Chemotherapy, radiotherapy or any investigational therapy within 4 weeks of study entry

• Current use or anticipated need for drugs that are known CYP34 inhibitors or inducers.

• Patients with carcinomatous meningitis or un-treated brain metastases.

• Any acute cardiovascular incident within the past 12 months.

• Patients with active gastrointestinal bleeding or significant gastrointestinal abnormalities as defined by protocol

• Patients with no evidence of the following for 5 years: malignancy or metastatic disease of skin cancer (except melanoma), in situ cervical cancer or breast cancer or T1C prostate cancer.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Detroit	Michigan	United States	48201
2	Pfizer Investigational Site	Detroit	Michigan	United States	48202
3	Pfizer Investigational Site	Madison	Wisconsin	United States	53792

Sponsors and Collaborators

• Pfizer
• University of Wisconsin, Madison

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: NCT01105533
• Other Study ID Numbers: A8051001
• First Posted: Apr 16, 2010
• Last Update Posted: Mar 19, 2013
• Last Verified: Feb 1, 2013

• Keywords provided by Pfizer: VGEF inhibitor; Anti angiogenesis; Advanced Solid Tumors

Study Results

Participant Flow

Arm/Group Title	PF-00337210 0.67 mg Once Daily	PF-00337210 1 mg Once Daily	PF-00337210 2 mg Once Daily	PF-00337210 4 mg Once Daily	PF-00337210 6 mg Once Daily	PF-00337210 8 mg Once Daily	PF-00337210 9 mg Once Daily	PF-00337210 4 mg Twice Daily	PF-00337210 6 mg Twice Daily
Arm/Group Description	PF-00337210 0.67 milligram (mg) capsule orally once daily in cycles of 28 days.	PF-00337210 1 mg capsule orally once daily in cycles of 28 days.	PF-00337210 2 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally once daily in cycles of 28 days.	PF-00337210 6 mg capsule orally once daily in cycles of 28 days.	PF-00337210 8 mg capsule orally once daily in cycles of 28 days.	PF-00337210 9 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally twice daily in cycles of 28 days.	PF-00337210 6 mg capsule orally twice daily in cycles of 28 days.
Period Title: Overall Study
STARTED	1	1	3	3	7	7	8	4	12
COMPLETED	0	0	0	0	0	0	0	0	0
NOT COMPLETED	1	1	3	3	7	7	8	4	12

Baseline Characteristics

Arm/Group Title	PF-00337210
Arm/Group Description	PF-00337210 0.67 mg, 1 mg, 2 mg, 4 mg, 6 mg, 8 mg or 9 mg capsule orally once daily or PF-00337210 4 mg or 6 mg capsule twice daily in cycles of 28 days.
Overall Participants	46
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.9 (13.1)
Sex: Female, Male (Count of Participants)
Female	21 45.7%
Male	25 54.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose-limiting Toxicities (DLTs)
Description	DLTs included events occurring in Cycle 1: blood pressure of 180/110 millimeters of mercury (mmHg) or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or greater than (>) 160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia for greater than or equal to (>=) 7 days or >=Grade 3 neutropenia associated with fever (1 reading of oral temperature >38.5 degree Celsius [degree C] or 3 readings of oral temperature >38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of >1/2 teaspoon of bright red blood per day; proteinuria of >=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; >=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.
Time Frame	Baseline up to Day 28

Outcome Measure Data

Analysis Population Description

Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	PF-00337210 0.67 mg Once Daily	PF-00337210 1 mg Once Daily	PF-00337210 2 mg Once Daily	PF-00337210 4 mg Once Daily	PF-00337210 6 mg Once Daily	PF-00337210 8 mg Once Daily	PF-00337210 9 mg Once Daily	PF-00337210 4 mg Twice Daily	PF-00337210 6 mg Twice Daily
Arm/Group Description	PF-00337210 0.67 milligram (mg) capsule orally once daily in cycles of 28 days.	PF-00337210 1 mg capsule orally once daily in cycles of 28 days.	PF-00337210 2 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally once daily in cycles of 28 days.	PF-00337210 6 mg capsule orally once daily in cycles of 28 days.	PF-00337210 8 mg capsule orally once daily in cycles of 28 days.	PF-00337210 9 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally twice daily in cycles of 28 days.	PF-00337210 6 mg capsule orally twice daily in cycles of 28 days.
Measure Participants	1	1	3	3	6	6	5	4	12
Number [participants]	0 0%	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN	2 NaN	0 NaN	1 NaN

2. Primary Outcome

Title	Maximum Tolerated Dose (MTD)
Description	MTD: dose level at which no more than 1 of 6 participants experienced DLT during Cycle 1. DLTs: blood pressure of 180/110 mmHg or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or >160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia >=7 days or >= Grade 3 neutropenia associated with fever (1 reading of oral temperature >38.5 degree C or 3 readings of oral temperature >38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of >1/2 teaspoon of bright red blood per day; proteinuria of >=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; >=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

Arm/Group Title	PF-00337210
Arm/Group Description	PF-00337210 0.67 mg, 1 mg, 2 mg, 4 mg, 6 mg, 8 mg or 9 mg capsule orally once daily or PF-00337210 4 mg or 6 mg capsule twice daily in cycles of 28 days.
Measure Participants	46
Number [mg once daily]	8

3. Primary Outcome

Title	Maximum Administered Dose (MAD)
Description	MAD: dose level at which 2 or more out of 6 participants experienced DLT during Cycle 1. DLTs: blood pressure of 180/110 mmHg or higher for 3 readings over 3 hours regardless of use of anti-hypertensive drugs or >160/100 mmHg for 3 readings over 3 days on maximum anti-hypertensive drugs; afebrile Grade 4 neutropenia >=7 days or >= Grade 3 neutropenia associated with fever (1 reading of oral temperature >38.5 degree C or 3 readings of oral temperature >38.0 degree C in 24-hour period); Grade 4 thrombocytopenia; hemoptysis of >1/2 teaspoon of bright red blood per day; proteinuria of >=2 grams/24 hours; inability to resume PF-00337210 dosing at current dose level within 14 days of stopping due to treatment-related toxicity; >=Grade 3 nonhematological toxicities (except alopecia and blood pressure/hypertension); Grade 3 nonhematological toxicities that could be controlled to Grade 2 or less with appropriate treatment were not considered dose limiting.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

Arm/Group Title	PF-00337210
Arm/Group Description	PF-00337210 0.67 mg, 1 mg, 2 mg, 4 mg, 6 mg, 8 mg or 9 mg capsule orally once daily or PF-00337210 4 mg or 6 mg capsule twice daily in cycles of 28 days.
Measure Participants	46
Number [mg once daily]	9

4. Primary Outcome

Title	Recommended Phase-2 Dose (RP2D)
Description	RP2D was determined based on the safety profile and pharmacodynamic findings. The twice daily dosing was preferred over once daily dosing for RP2D, as per investigator's discretion, due to more consistent changes in pharmacodynamic markers and greater clinical benefit observed in twice daily dosing.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Safety analysis set included all enrolled participants who received at least 1 dose of study medication.

Arm/Group Title	PF-00337210
Arm/Group Description	PF-00337210 0.67 mg, 1 mg, 2 mg, 4 mg, 6 mg, 8 mg or 9 mg capsule orally once daily or PF-00337210 4 mg or 6 mg capsule twice daily in cycles of 28 days.
Measure Participants	46
Number [mg twice daily]	6

5. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax)
Time Frame	Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hours(hrs) post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57

Outcome Measure Data

Analysis Population Description

Formal quality-assured, quality-controlled, pharmacokinetic (PK) analysis was not performed and hence, Cmax was not calculated.

Arm/Group Title	PF-00337210 0.67 mg Once Daily	PF-00337210 1 mg Once Daily	PF-00337210 2 mg Once Daily	PF-00337210 4 mg Once Daily	PF-00337210 6 mg Once Daily	PF-00337210 8 mg Once Daily	PF-00337210 9 mg Once Daily	PF-00337210 4 mg Twice Daily	PF-00337210 6 mg Twice Daily
Arm/Group Description	PF-00337210 0.67 milligram (mg) capsule orally once daily in cycles of 28 days.	PF-00337210 1 mg capsule orally once daily in cycles of 28 days.	PF-00337210 2 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally once daily in cycles of 28 days.	PF-00337210 6 mg capsule orally once daily in cycles of 28 days.	PF-00337210 8 mg capsule orally once daily in cycles of 28 days.	PF-00337210 9 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally twice daily in cycles of 28 days.	PF-00337210 6 mg capsule orally twice daily in cycles of 28 days.
Measure Participants	0	0	0	0	0	0	0	0	0

6. Secondary Outcome

Title	Plasma Decay Half-Life (t1/2)
Description	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time Frame	Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57

Outcome Measure Data

Analysis Population Description

Formal quality-assured, quality-controlled, pharmacokinetic (PK) analysis was not performed and hence, t1/2 was not calculated.

Arm/Group Title	PF-00337210 0.67 mg Once Daily	PF-00337210 1 mg Once Daily	PF-00337210 2 mg Once Daily	PF-00337210 4 mg Once Daily	PF-00337210 6 mg Once Daily	PF-00337210 8 mg Once Daily	PF-00337210 9 mg Once Daily	PF-00337210 4 mg Twice Daily	PF-00337210 6 mg Twice Daily
Arm/Group Description	PF-00337210 0.67 milligram (mg) capsule orally once daily in cycles of 28 days.	PF-00337210 1 mg capsule orally once daily in cycles of 28 days.	PF-00337210 2 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally once daily in cycles of 28 days.	PF-00337210 6 mg capsule orally once daily in cycles of 28 days.	PF-00337210 8 mg capsule orally once daily in cycles of 28 days.	PF-00337210 9 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally twice daily in cycles of 28 days.	PF-00337210 6 mg capsule orally twice daily in cycles of 28 days.
Measure Participants	0	0	0	0	0	0	0	0	0

7. Secondary Outcome

Title	Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)]
Description	AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).
Time Frame	Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57

Outcome Measure Data

Analysis Population Description

Formal quality-assured, quality-controlled, pharmacokinetic (PK) analysis was not performed and hence, AUC (0-24) was not calculated.

Arm/Group Title	PF-00337210 0.67 mg Once Daily	PF-00337210 1 mg Once Daily	PF-00337210 2 mg Once Daily	PF-00337210 4 mg Once Daily	PF-00337210 6 mg Once Daily	PF-00337210 8 mg Once Daily	PF-00337210 9 mg Once Daily	PF-00337210 4 mg Twice Daily	PF-00337210 6 mg Twice Daily
Arm/Group Description	PF-00337210 0.67 milligram (mg) capsule orally once daily in cycles of 28 days.	PF-00337210 1 mg capsule orally once daily in cycles of 28 days.	PF-00337210 2 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally once daily in cycles of 28 days.	PF-00337210 6 mg capsule orally once daily in cycles of 28 days.	PF-00337210 8 mg capsule orally once daily in cycles of 28 days.	PF-00337210 9 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally twice daily in cycles of 28 days.	PF-00337210 6 mg capsule orally twice daily in cycles of 28 days.
Measure Participants	0	0	0	0	0	0	0	0	0

8. Secondary Outcome

Title	Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0 - ∞)]
Description	AUC (0 - ∞)= Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞). It is obtained from AUC (0 - t) plus AUC (t - ∞).
Time Frame	Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57

Outcome Measure Data

Analysis Population Description

Formal quality-assured, quality-controlled, pharmacokinetic (PK) analysis was not performed and hence, AUC (0 - ∞) was not calculated.

Arm/Group Title	PF-00337210 0.67 mg Once Daily	PF-00337210 1 mg Once Daily	PF-00337210 2 mg Once Daily	PF-00337210 4 mg Once Daily	PF-00337210 6 mg Once Daily	PF-00337210 8 mg Once Daily	PF-00337210 9 mg Once Daily	PF-00337210 4 mg Twice Daily	PF-00337210 6 mg Twice Daily
Arm/Group Description	PF-00337210 0.67 milligram (mg) capsule orally once daily in cycles of 28 days.	PF-00337210 1 mg capsule orally once daily in cycles of 28 days.	PF-00337210 2 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally once daily in cycles of 28 days.	PF-00337210 6 mg capsule orally once daily in cycles of 28 days.	PF-00337210 8 mg capsule orally once daily in cycles of 28 days.	PF-00337210 9 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally twice daily in cycles of 28 days.	PF-00337210 6 mg capsule orally twice daily in cycles of 28 days.
Measure Participants	0	0	0	0	0	0	0	0	0

9. Secondary Outcome

Title	Apparent Volume of Distribution (Vss)
Description	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 is influenced by the fraction absorbed.
Time Frame	Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57

Outcome Measure Data

Analysis Population Description

Formal quality-assured, quality-controlled, pharmacokinetic (PK) analysis was not performed and hence, Vss was not calculated.

Arm/Group Title	PF-00337210 0.67 mg Once Daily	PF-00337210 1 mg Once Daily	PF-00337210 2 mg Once Daily	PF-00337210 4 mg Once Daily	PF-00337210 6 mg Once Daily	PF-00337210 8 mg Once Daily	PF-00337210 9 mg Once Daily	PF-00337210 4 mg Twice Daily	PF-00337210 6 mg Twice Daily
Arm/Group Description	PF-00337210 0.67 milligram (mg) capsule orally once daily in cycles of 28 days.	PF-00337210 1 mg capsule orally once daily in cycles of 28 days.	PF-00337210 2 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally once daily in cycles of 28 days.	PF-00337210 6 mg capsule orally once daily in cycles of 28 days.	PF-00337210 8 mg capsule orally once daily in cycles of 28 days.	PF-00337210 9 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally twice daily in cycles of 28 days.	PF-00337210 6 mg capsule orally twice daily in cycles of 28 days.
Measure Participants	0	0	0	0	0	0	0	0	0

10. Secondary Outcome

Title	Systemic Clearance (CL)
Description	CL is a quantitative measure of the rate at which a drug substance is removed from the body.
Time Frame	Pre-dose,0.5,1,2,4,6,8,10,16,20,24 hrs post-dose on Day 1(0.67 mg group);pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 1,15,29(once daily groups);pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 1,15,29 (twice daily groups);pre-dose on Day 43, 57

Outcome Measure Data

Analysis Population Description

Formal quality-assured, quality-controlled, PK analysis was not performed and hence, CL was not calculated.

Arm/Group Title	PF-00337210 0.67 mg Once Daily	PF-00337210 1 mg Once Daily	PF-00337210 2 mg Once Daily	PF-00337210 4 mg Once Daily	PF-00337210 6 mg Once Daily	PF-00337210 8 mg Once Daily	PF-00337210 9 mg Once Daily	PF-00337210 4 mg Twice Daily	PF-00337210 6 mg Twice Daily
Arm/Group Description	PF-00337210 0.67 milligram (mg) capsule orally once daily in cycles of 28 days.	PF-00337210 1 mg capsule orally once daily in cycles of 28 days.	PF-00337210 2 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally once daily in cycles of 28 days.	PF-00337210 6 mg capsule orally once daily in cycles of 28 days.	PF-00337210 8 mg capsule orally once daily in cycles of 28 days.	PF-00337210 9 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally twice daily in cycles of 28 days.	PF-00337210 6 mg capsule orally twice daily in cycles of 28 days.
Measure Participants	0	0	0	0	0	0	0	0	0

11. Secondary Outcome

Title	Number of Participants With Objective Response of Complete Response or Partial Response
Description	Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target and non-target lesions and no appearance of new lesions. Confirmed PR defined as at least 30 percent decrease in sum of the longest dimensions (LD) of the target lesions, taking as a reference the baseline sum LD, without progression of non-target lesions and no appearance of new lesions. Confirmed responses are those that persist on repeat imaging study >=4 weeks after initial documentation of response.
Time Frame	Baseline, every 8 weeks up to Cycle 25 (Week 100)

Outcome Measure Data

Analysis Population Description

Full Analysis set included all enrolled participants who received at least 1 dose of study medication.

Arm/Group Title	PF-00337210
Arm/Group Description	PF-00337210 0.67 mg, 1 mg, 2 mg, 4 mg, 6 mg, 8 mg or 9 mg capsule orally once daily or PF-00337210 4 mg or 6 mg capsule twice daily in cycles of 28 days.
Measure Participants	46
Number [participants]	2 4.3%

12. Secondary Outcome

Title	Change From Baseline in Biomarkers at Day 1 of Each Cycle up to Cycle 25
Description	Biomarkers included soluble plasma proteins associated with angiogenesis (vascular endothelial growth factor [VEGF], soluble vascular endothelial growth factor-2 receptor [sVEGFR2], soluble vascular endothelial growth factor-3 receptor [sVEGFR3], soluble beta type platelet-derived growth factor [sPDGFR beta]) and tumor proliferation (soluble stem-cell factor receptor [sKIT])
Time Frame	Baseline, Day 1 of Cycle 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25

Outcome Measure Data

Analysis Population Description

Results are not reported as the data were not statistically summarized but available in individual participant listing.

Arm/Group Title	PF-00337210 0.67 mg Once Daily	PF-00337210 1 mg Once Daily	PF-00337210 2 mg Once Daily	PF-00337210 4 mg Once Daily	PF-00337210 6 mg Once Daily	PF-00337210 8 mg Once Daily	PF-00337210 9 mg Once Daily	PF-00337210 4 mg Twice Daily	PF-00337210 6 mg Twice Daily
Arm/Group Description	PF-00337210 0.67 milligram (mg) capsule orally once daily in cycles of 28 days.	PF-00337210 1 mg capsule orally once daily in cycles of 28 days.	PF-00337210 2 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally once daily in cycles of 28 days.	PF-00337210 6 mg capsule orally once daily in cycles of 28 days.	PF-00337210 8 mg capsule orally once daily in cycles of 28 days.	PF-00337210 9 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally twice daily in cycles of 28 days.	PF-00337210 6 mg capsule orally twice daily in cycles of 28 days.
Measure Participants	0	0	0	0	0	0	0	0	0

13. Other Pre-specified Outcome

Title	Effect of Food on Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-24)]
Description	AUC (0-24)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-24).
Time Frame	Pre-dose,0.5,1,2,4,6,8,18,20,24 hrs post-dose on Day 29 (fasted state), Day 30 (fed state) for once daily groups, pre-dose,0.5,1,2,4,6,8 hrs post-dose on Day 29 Day 29 (fasted state), Day 30 (fed state) for twice daily groups

Outcome Measure Data

Analysis Population Description

Formal quality-assured, quality-controlled, PK analysis was not performed and hence, food effect on AUC (0-24) was not assessed.

Arm/Group Title	PF-00337210 0.67 mg Once Daily	PF-00337210 1 mg Once Daily	PF-00337210 2 mg Once Daily	PF-00337210 4 mg Once Daily	PF-00337210 6 mg Once Daily	PF-00337210 8 mg Once Daily	PF-00337210 9 mg Once Daily	PF-00337210 4 mg Twice Daily	PF-00337210 6 mg Twice Daily
Arm/Group Description	PF-00337210 0.67 milligram (mg) capsule orally once daily in cycles of 28 days.	PF-00337210 1 mg capsule orally once daily in cycles of 28 days.	PF-00337210 2 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally once daily in cycles of 28 days.	PF-00337210 6 mg capsule orally once daily in cycles of 28 days.	PF-00337210 8 mg capsule orally once daily in cycles of 28 days.	PF-00337210 9 mg capsule orally once daily in cycles of 28 days.	PF-00337210 4 mg capsule orally twice daily in cycles of 28 days.	PF-00337210 6 mg capsule orally twice daily in cycles of 28 days.
Measure Participants	0	0	0	0	0	0	0	0	0

Adverse Events

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-00337210
Arm/Group Description	PF-00337210 0.67 mg, 1 mg, 2 mg, 4 mg, 6 mg, 8 mg or 9 mg capsule orally once daily or PF-00337210 4 mg or 6 mg capsule twice daily in cycles of 28 days.
All Cause Mortality
	PF-00337210
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	PF-00337210
	Affected / at Risk (%)	# Events
Total	19/46 (41.3%)
Blood and lymphatic system disorders
Leukocytosis	1/46 (2.2%)
Polycythaemia	1/46 (2.2%)
Cardiac disorders
Atrial fibrillation	1/46 (2.2%)
Myocardial ischaemia	1/46 (2.2%)
Palpitations	1/46 (2.2%)
Gastrointestinal disorders
Abdominal pain	1/46 (2.2%)
Dysphagia	1/46 (2.2%)
Gastrointestinal haemorrhage	1/46 (2.2%)
Ileus	1/46 (2.2%)
Nausea	1/46 (2.2%)
Small intestinal obstruction	1/46 (2.2%)
Vomiting	2/46 (4.3%)
General disorders
Asthenia	1/46 (2.2%)
Disease progression	4/46 (8.7%)
Fatigue	2/46 (4.3%)
Pain	1/46 (2.2%)
Infections and infestations
Oesophageal candidiasis	1/46 (2.2%)
Pneumonia	2/46 (4.3%)
Investigations
Alanine aminotransferase increased	2/46 (4.3%)
Aspartate aminotransferase increased	2/46 (4.3%)
Blood alkaline phosphatase increased	1/46 (2.2%)
Blood bilirubin increased	2/46 (4.3%)
Electrocardiogram abnormal	1/46 (2.2%)
Metabolism and nutrition disorders
Dehydration	4/46 (8.7%)
Hyperkalaemia	1/46 (2.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage	1/46 (2.2%)
Nervous system disorders
Depressed level of consciousness	1/46 (2.2%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/46 (2.2%)
Pneumonia aspiration	1/46 (2.2%)
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome	2/46 (4.3%)
Vascular disorders
Hypertension	1/46 (2.2%)
Hypotension	1/46 (2.2%)
Other (Not Including Serious) Adverse Events
	PF-00337210
	Affected / at Risk (%)	# Events
Total	46/46 (100%)
Blood and lymphatic system disorders
Anaemia	1/46 (2.2%)
Leukopenia	1/46 (2.2%)
Neutropenia	2/46 (4.3%)
Thrombocytopenia	2/46 (4.3%)
Cardiac disorders
Palpitations	2/46 (4.3%)
Ear and labyrinth disorders
Ear congestion	1/46 (2.2%)
Ear discomfort	1/46 (2.2%)
Ear disorder	1/46 (2.2%)
Eye disorders
Dry eye	1/46 (2.2%)
Eye swelling	1/46 (2.2%)
Periorbital oedema	1/46 (2.2%)
Gastrointestinal disorders
Abdominal distension	3/46 (6.5%)
Abdominal pain	10/46 (21.7%)
Abdominal pain lower	4/46 (8.7%)
Abdominal pain upper	2/46 (4.3%)
Anal haemorrhage	1/46 (2.2%)
Ascites	3/46 (6.5%)
Constipation	5/46 (10.9%)
Diarrhoea	18/46 (39.1%)
Dry mouth	4/46 (8.7%)
Dyspepsia	8/46 (17.4%)
Eructation	1/46 (2.2%)
Faecal incontinence	1/46 (2.2%)
Flatulence	1/46 (2.2%)
Gastrointestinal haemorrhage	1/46 (2.2%)
Gastrooesophageal reflux disease	3/46 (6.5%)
Haematochezia	1/46 (2.2%)
Haemorrhoidal haemorrhage	1/46 (2.2%)
Nausea	18/46 (39.1%)
Oesophageal pain	1/46 (2.2%)
Oral pain	1/46 (2.2%)
Retching	1/46 (2.2%)
Small intestinal obstruction	1/46 (2.2%)
Stomatitis	2/46 (4.3%)
Tongue exfoliation	1/46 (2.2%)
Toothache	1/46 (2.2%)
Vomiting	6/46 (13%)
General disorders
Chest discomfort	3/46 (6.5%)
Chest pain	6/46 (13%)
Chills	5/46 (10.9%)
Early satiety	1/46 (2.2%)
Fatigue	23/46 (50%)
Feeling cold	1/46 (2.2%)
Induration	1/46 (2.2%)
Localised oedema	1/46 (2.2%)
Mucosal inflammation	2/46 (4.3%)
Oedema	3/46 (6.5%)
Pain	3/46 (6.5%)
Pyrexia	6/46 (13%)
Hepatobiliary disorders
Bile duct obstruction	1/46 (2.2%)
Cholangitis	1/46 (2.2%)
Hepatomegaly	1/46 (2.2%)
Immune system disorders
Multiple allergies	1/46 (2.2%)
Seasonal allergy	1/46 (2.2%)
Infections and infestations
Abdominal abscess	1/46 (2.2%)
Bronchitis	1/46 (2.2%)
Candidiasis	1/46 (2.2%)
Gastroenteritis viral	1/46 (2.2%)
Herpes zoster	1/46 (2.2%)
Infection	2/46 (4.3%)
Nasopharyngitis	2/46 (4.3%)
Pharyngitis	1/46 (2.2%)
Pneumonia	1/46 (2.2%)
Respiratory tract infection viral	1/46 (2.2%)
Sepsis	1/46 (2.2%)
Sinusitis	1/46 (2.2%)
Upper respiratory tract infection	1/46 (2.2%)
Urinary tract infection	5/46 (10.9%)
Injury, poisoning and procedural complications
Eye injury	1/46 (2.2%)
Wound	1/46 (2.2%)
Wound necrosis	1/46 (2.2%)
Investigations
Activated partial thromboplastin time prolonged	1/46 (2.2%)
Alanine aminotransferase	1/46 (2.2%)
Alanine aminotransferase increased	4/46 (8.7%)
Aspartate aminotransferase increased	8/46 (17.4%)
Band neutrophil count increased	1/46 (2.2%)
Blood albumin decreased	1/46 (2.2%)
Blood alkaline phosphatase	1/46 (2.2%)
Blood alkaline phosphatase increased	4/46 (8.7%)
Blood bilirubin increased	2/46 (4.3%)
Blood calcium decreased	1/46 (2.2%)
Blood creatinine increased	2/46 (4.3%)
Blood lactate dehydrogenase increased	1/46 (2.2%)
Blood magnesium decreased	1/46 (2.2%)
Blood potassium decreased	1/46 (2.2%)
Blood pressure increased	1/46 (2.2%)
Blood urea increased	1/46 (2.2%)
Breath sounds abnormal	1/46 (2.2%)
Carbon dioxide decreased	1/46 (2.2%)
Electrocardiogram QT prolonged	1/46 (2.2%)
Eosinophil count increased	1/46 (2.2%)
Haemoglobin decreased	3/46 (6.5%)
International normalised ratio increased	1/46 (2.2%)
Monocyte count increased	1/46 (2.2%)
Neutrophil count	2/46 (4.3%)
Neutrophil count decreased	2/46 (4.3%)
Neutrophil count increased	1/46 (2.2%)
Troponin I increased	1/46 (2.2%)
Weight decreased	8/46 (17.4%)
White blood cell count	1/46 (2.2%)
White blood cell count decreased	2/46 (4.3%)
Metabolism and nutrition disorders
Decreased appetite	11/46 (23.9%)
Dehydration	4/46 (8.7%)
Hyperglycaemia	5/46 (10.9%)
Hyperkalaemia	1/46 (2.2%)
Hypoglycaemia	1/46 (2.2%)
Hypokalaemia	4/46 (8.7%)
Hyponatraemia	4/46 (8.7%)
Hypophagia	2/46 (4.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/46 (10.9%)
Back pain	10/46 (21.7%)
Flank pain	1/46 (2.2%)
Joint swelling	1/46 (2.2%)
Joint warmth	1/46 (2.2%)
Muscle spasms	1/46 (2.2%)
Muscle tightness	1/46 (2.2%)
Musculoskeletal chest pain	6/46 (13%)
Musculoskeletal pain	8/46 (17.4%)
Myalgia	5/46 (10.9%)
Neck pain	2/46 (4.3%)
Nodule on extremity	1/46 (2.2%)
Pain in extremity	6/46 (13%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin neoplasm bleeding	1/46 (2.2%)
Tumour pain	2/46 (4.3%)
Nervous system disorders
Dizziness	9/46 (19.6%)
Dyskinesia	1/46 (2.2%)
Headache	9/46 (19.6%)
Hypoaesthesia	1/46 (2.2%)
Neuropathy peripheral	1/46 (2.2%)
Paraesthesia	1/46 (2.2%)
Peripheral sensory neuropathy	2/46 (4.3%)
Post herpetic neuralgia	1/46 (2.2%)
Restless legs syndrome	1/46 (2.2%)
Sciatica	2/46 (4.3%)
Sensory disturbance	1/46 (2.2%)
Syncope	1/46 (2.2%)
Psychiatric disorders
Anxiety	1/46 (2.2%)
Depression	2/46 (4.3%)
Insomnia	1/46 (2.2%)
Mental status changes	2/46 (4.3%)
Renal and urinary disorders
Dysuria	3/46 (6.5%)
Haematuria	1/46 (2.2%)
Pollakiuria	2/46 (4.3%)
Proteinuria	11/46 (23.9%)
Urine odour abnormal	1/46 (2.2%)
Urogenital haemorrhage	1/46 (2.2%)
Reproductive system and breast disorders
Breast discomfort	1/46 (2.2%)
Breast disorder	1/46 (2.2%)
Ejaculation disorder	1/46 (2.2%)
Respiratory, thoracic and mediastinal disorders
Bronchospasm	1/46 (2.2%)
Cough	9/46 (19.6%)
Dysphonia	5/46 (10.9%)
Dyspnoea	8/46 (17.4%)
Dyspnoea exertional	1/46 (2.2%)
Epistaxis	1/46 (2.2%)
Hiccups	2/46 (4.3%)
Increased upper airway secretion	1/46 (2.2%)
Nasal congestion	1/46 (2.2%)
Oropharyngeal pain	7/46 (15.2%)
Paranasal sinus hypersecretion	1/46 (2.2%)
Pharyngeal erythema	1/46 (2.2%)
Pleural effusion	2/46 (4.3%)
Productive cough	2/46 (4.3%)
Rhinalgia	1/46 (2.2%)
Rhinitis allergic	8/46 (17.4%)
Rhinorrhoea	1/46 (2.2%)
Throat irritation	1/46 (2.2%)
Upper-airway cough syndrome	2/46 (4.3%)
Vocal cord disorder	1/46 (2.2%)
Skin and subcutaneous tissue disorders
Acne	1/46 (2.2%)
Blood blister	1/46 (2.2%)
Dermatitis allergic	1/46 (2.2%)
Dry skin	2/46 (4.3%)
Erythema	2/46 (4.3%)
Hyperhidrosis	6/46 (13%)
Nail disorder	1/46 (2.2%)
Night sweats	3/46 (6.5%)
Palmar-plantar erythrodysaesthesia syndrome	2/46 (4.3%)
Photosensitivity reaction	1/46 (2.2%)
Pruritus	3/46 (6.5%)
Rash	7/46 (15.2%)
Skin disorder	1/46 (2.2%)
Skin lesion	2/46 (4.3%)
Skin nodule	1/46 (2.2%)
Vascular disorders
Flushing	3/46 (6.5%)
Hot flush	6/46 (13%)
Hypertension	24/46 (52.2%)
Phlebitis	1/46 (2.2%)

Limitations/Caveats

Designation of outcomes as primary and secondary was based on study team input as study did not specify primary or secondary outcome measures.

More Information

Certain Agreements

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.