Study Evaluating SKI-606 (Bosutinib) In Subjects With Breast Cancer

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00319254
• Collaborator: (none)
• Enrollment: 75
• Locations: 15
• Arm: 1
• Duration (Months): 33.1
• Patients Per Site: 5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine if SKI-606 (Bosutinib) is effective in the treatment of advanced or metastatic breast cancer. Patients must have current Stage IIIB, IIIC or IV breast cancer and have progressed after 1 to 3 prior chemotherapy regimens.

Condition or Disease	Intervention/Treatment	Phase
Breast Neoplasms; Neoplasm Metastasis	Drug: SKI-606 (Bosutinib)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study Of SKI-606 In Subjects With Advanced Or Metastatic Breast Cancer
• Study Start Date: May 1, 2006
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Advanced breast cancer	Drug: SKI-606 (Bosutinib); SKI-606 (Bosutinib) 400mg once daily, for as long as tolerated or until disease progression.

Outcome Measures

Primary Outcome Measures

1. Progression-Free Survival (PFS) Rate [Baseline up to Week 16]

   PFS was based on Kaplan-Meier estimates. PFS was defined as time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from death case report forms (CRFs). Percentage of participants who had not experienced progression or death by Week 16 is reported.

2. Percentage of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs) [Baseline up to 30 days after last dose of study treatment]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.

Secondary Outcome Measures

1. Overall Survival (OS) [Baseline up to Year 2]

   OS was estimated by Kaplan-Meier method. Survival was defined as the time period from the date of first dose of study treatment to the date of death, censored at the participant's last contact date. Percentage of participants who were still alive at 2 years is reported.

2. Percentage of Participants With Objective Response (OR) [Baseline up to Year 1]

   Percentage of participants with OR was based on the assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to sponsor modified Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target and non-target lesions. Confirmed PR defined as more than or equal to (>=) 30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD. Confirmed responses are those that persist on repeat imaging study >=4 weeks after initial documentation of response.

3. Percentage of Participants With Clinical Benefit [Baseline up to end of treatment (Week 77)]

   Clinical benefit was defined as a confirmed CR or PR, or stable disease (SD) for more than (>) 24 weeks as the best response before the first evidence of progressive disease (PD). A participant demonstrating CR, PR, or SD >24 weeks at any time while on study was counted in the numerator.

4. Number of Participants With Change From Baseline in Laboratory Test Results [Baseline up to end of treatment (Week 77)]

   Number of participants with potentially clinically significant (PCS) laboratory values are reported. Criteria for PCS laboratory values include: aspartate aminotransferase (AST), alanine aminotransferase (ALT) >5*upper limit of normal(ULN) milliunit/milliliter(mU/mL); total bilirubin >3*ULN micromole/L; sodium <130, magnesium <0.4 and >1.23 millimole/L; lipase >2*ULN microkats/L; neutrophils <1*10^9/L. Participants meeting at least 1 PCS criteria are reported.

5. Number of Participants With Change From Baseline in Electrocardiogram (ECG) [Baseline up to end of treatment (Week 77)]

   Number of participants with potentially clinically significant (PCS) ECG findings are reported. Criteria for PCS ECG findings include: no sinus rhythm; heart rate >=120 beats per minute (bpm) or increase >=15 bpm; QT interval corrected using Bazett's formula (QTcB) >60 milliseconds (msec) change from baseline; and overall ECG evaluation not normal.

6. Number of Participants With Change From Baseline in Vital Signs, Physical Examinations, and Ophthalmological Examinations [Baseline up to end of treatment (Week 77)]

   Number of participants with potentially clinically significant (PCS) vital signs and physical examinations are reported. Criteria for PCS vital signs include: respiratory rate >25 breaths/minute and PCS physical examinations include: an increase or decrease from baseline of >=7% in body weight.

7. Concomitant Medications Used for Management of Adverse Events (AEs) [Day 1 up to end of treatment (Week 77)]

   Number of participants taking any non-study medications which were administered from Study Day 1 to last dose of study treatment (Week 77) as a management of an AE were to be reported.

8. Change From Baseline in Karnofsky Performance Status (KPS) at Week 1, 4, 8, 12, 16, Every 8 Weeks Thereafter and 14 Days After Last Dose of Study Treatment [Baseline, Weeks 1,4,8,12,16, every 8 weeks thereafter and 14 days after last dose of study treatment]

   KPS: 11 level score ranged 100 to 0, to assess functional impairment. 100:Normal; 90:Able to carry on normal activity; 80:Normal activity with effort, some signs or symptoms of disease; 70:Cares for self, unable to carry on normal activity or to do active work; 60:Requires occasional assistance but is able to care for most of needs; 50:Requires considerable assistance and frequent medical care; 40:Disabled,requires special care and assistance; 30:Severely disabled; hospitalization indicated although death is not imminent; 20:Very sick; 10:Morbibund,fatal processes progressing rapidly; 0:Death.

Other Outcome Measures

1. Population Pharmacokinetics (PK) [Pre-dose, 2, 7, 20 hours post-dose on Day 1 of Week 4 and pre-dose on Day 1 of Weeks 1, 8, 12, 16, and 24]

   Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Stage IIIB, IIIC or IV breast cancer not curable with available therapy.

• Patients must have progressed after 1 but not more than 3 prior chemotherapy regimens.

• Life expectancy of at least 16 weeks.

• Ability to swallow whole capsules.

Exclusion Criteria:

• Use of or requirement for bisphosphonates within 8 weeks prior to screening.

• Any other cancer within 5 years of screening, except for basal cell carcinoma or cervical carcinoma in situ

• Uncontrolled cardiac disease including congestive heart failure, angina, heart attack, etc.

• Recent or ongoing significant gastrointestinal disorder

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Duarte	California	United States	91010-3000
2	Pfizer Investigational Site	Santa Monica	California	United States	90404
3	Pfizer Investigational Site	Tampa	Florida	United States	33612
4	Pfizer Investigational Site	Cleveland	Ohio	United States	44195
5	Pfizer Investigational Site	Darlinghurst	New South Wales	Australia	2010
6	Pfizer Investigational Site	Dijon		France	21034
7	Pfizer Investigational Site	Saint-Herblain		France	44805
8	Pfizer Investigational Site	Pokfulam		Hong Kong
9	Pfizer Investigational Site	Floriana		Malta	VLT 14
10	Pfizer Investigational Site	Lodz		Poland	90-553
11	Pfizer Investigational Site	Wroclaw		Poland	51-124
12	Pfizer Investigational Site	Moscow		Russian Federation	115478
13	Pfizer Investigational Site	Dnipropetrovsk		Ukraine	49102
14	Pfizer Investigational Site	Sumy		Ukraine	40005
15	Pfizer Investigational Site	Uzhgorod		Ukraine	88014

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: NCT00319254
• Other Study ID Numbers: 3160A2-201; B1871014
• First Posted: Apr 27, 2006
• Last Update Posted: Jan 31, 2013
• Last Verified: Dec 1, 2012

• Keywords provided by Pfizer: Advanced Breast Cancer
• Additional relevant MeSH terms: Breast Neoplasms; Neoplasms; Neoplasm Metastasis

Study Results

Participant Flow

Arm/Group Title	Bosutinib
Arm/Group Description	Four bosutinib 100 milligram (mg) capsules, equivalent to 400 mg bosutinib orally once daily for 48 weeks, or until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Period Title: Overall Study
STARTED	75
Treated	73
COMPLETED	21
NOT COMPLETED	54

Baseline Characteristics

Arm/Group Title	Bosutinib
Arm/Group Description	Four bosutinib 100 milligram (mg) capsules, equivalent to 400 mg bosutinib orally once daily for 48 weeks, or until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Overall Participants	73
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.27 (9.81)
Sex: Female, Male (Count of Participants)
Female	73 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Progression-Free Survival (PFS) Rate
Description	PFS was based on Kaplan-Meier estimates. PFS was defined as time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from death case report forms (CRFs). Percentage of participants who had not experienced progression or death by Week 16 is reported.
Time Frame	Baseline up to Week 16

Outcome Measure Data

Analysis Population Description

Intent-To-Treat (ITT) population included all enrolled participants who received at least 1 dose of study treatment.

Arm/Group Title	Bosutinib
Arm/Group Description	Four bosutinib 100 milligram (mg) capsules, equivalent to 400 mg bosutinib orally once daily for 48 weeks, or until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Measure Participants	73
Number (95% Confidence Interval) [percentage of participants]	39.6 54.2%

2. Primary Outcome

Title	Percentage of Participants With Treatment-Emergent Adverse Events (AEs) And Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.
Time Frame	Baseline up to 30 days after last dose of study treatment

Outcome Measure Data

Analysis Population Description

Safety population included all enrolled participants who received at least 1 dose of study treatment.

Arm/Group Title	Bosutinib
Arm/Group Description	Four bosutinib 100 milligram (mg) capsules, equivalent to 400 mg bosutinib orally once daily for 48 weeks, or until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Measure Participants	73
AEs	97 132.9%
SAEs	33 45.2%

3. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was estimated by Kaplan-Meier method. Survival was defined as the time period from the date of first dose of study treatment to the date of death, censored at the participant's last contact date. Percentage of participants who were still alive at 2 years is reported.
Time Frame	Baseline up to Year 2

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants who received at least 1 dose of study treatment.

Arm/Group Title	Bosutinib
Arm/Group Description	Four bosutinib 100 milligram (mg) capsules, equivalent to 400 mg bosutinib orally once daily for 48 weeks, or until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Measure Participants	73
Number (95% Confidence Interval) [percentage of participants]	26.4 36.2%

4. Secondary Outcome

Title	Percentage of Participants With Objective Response (OR)
Description	Percentage of participants with OR was based on the assessment of confirmed complete remission (CR) or confirmed partial remission (PR) according to sponsor modified Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target and non-target lesions. Confirmed PR defined as more than or equal to (>=) 30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD. Confirmed responses are those that persist on repeat imaging study >=4 weeks after initial documentation of response.
Time Frame	Baseline up to Year 1

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants who received at least 1 dose of study treatment.

Arm/Group Title	Bosutinib
Arm/Group Description	Four bosutinib 100 milligram (mg) capsules, equivalent to 400 mg bosutinib orally once daily for 48 weeks, or until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Measure Participants	73
Number (95% Confidence Interval) [percentage of participants]	5.5 7.5%

5. Secondary Outcome

Title	Percentage of Participants With Clinical Benefit
Description	Clinical benefit was defined as a confirmed CR or PR, or stable disease (SD) for more than (>) 24 weeks as the best response before the first evidence of progressive disease (PD). A participant demonstrating CR, PR, or SD >24 weeks at any time while on study was counted in the numerator.
Time Frame	Baseline up to end of treatment (Week 77)

Outcome Measure Data

Analysis Population Description

ITT population included all enrolled participants who received at least 1 dose of study treatment.

Arm/Group Title	Bosutinib
Arm/Group Description	Four bosutinib 100 milligram (mg) capsules, equivalent to 400 mg bosutinib orally once daily for 48 weeks, or until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Measure Participants	73
Number (95% Confidence Interval) [percentage of participants]	27.4 37.5%

6. Secondary Outcome

Title	Number of Participants With Change From Baseline in Laboratory Test Results
Description	Number of participants with potentially clinically significant (PCS) laboratory values are reported. Criteria for PCS laboratory values include: aspartate aminotransferase (AST), alanine aminotransferase (ALT) >5*upper limit of normal(ULN) milliunit/milliliter(mU/mL); total bilirubin >3*ULN micromole/L; sodium <130, magnesium <0.4 and >1.23 millimole/L; lipase >2*ULN microkats/L; neutrophils <1*10^9/L. Participants meeting at least 1 PCS criteria are reported.
Time Frame	Baseline up to end of treatment (Week 77)

Outcome Measure Data

Analysis Population Description

Safety population included all enrolled participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) represents number of participants who had at least 1 on-treatment assessment.

Arm/Group Title	Bosutinib
Arm/Group Description	Four bosutinib 100 milligram (mg) capsules, equivalent to 400 mg bosutinib orally once daily for 48 weeks, or until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Measure Participants	68
Sodium (<130 mmol/L)	2 2.7%
Magnesium (<0.4 mmol/L)	3 4.1%
Magnesium (>1.23 mmol/L)	3 4.1%
Total Bilirubin (>3*ULN)	1 1.4%
ALT (>5*ULN)	12 16.4%
AST (>5*ULN)	10 13.7%
Lipase (>2*ULN)	1 1.4%
Neutrophils (<1*10^9/L)	1 1.4%

7. Secondary Outcome

Title	Number of Participants With Change From Baseline in Electrocardiogram (ECG)
Description	Number of participants with potentially clinically significant (PCS) ECG findings are reported. Criteria for PCS ECG findings include: no sinus rhythm; heart rate >=120 beats per minute (bpm) or increase >=15 bpm; QT interval corrected using Bazett's formula (QTcB) >60 milliseconds (msec) change from baseline; and overall ECG evaluation not normal.
Time Frame	Baseline up to end of treatment (Week 77)

Outcome Measure Data

Analysis Population Description

Safety population included all enrolled participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) represents number of participants who had at least 1 on-treatment assessment.

Arm/Group Title	Bosutinib
Arm/Group Description	Four bosutinib 100 milligram (mg) capsules, equivalent to 400 mg bosutinib orally once daily for 48 weeks, or until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Measure Participants	64
No sinus rhythm	12 16.4%
Heart Rate (>=120 bpm and increase >=15bpm)	2 2.7%
QTcB Interval (>60 msec change from baseline)	1 1.4%
Overall ECG not normal	12 16.4%

8. Secondary Outcome

Title	Number of Participants With Change From Baseline in Vital Signs, Physical Examinations, and Ophthalmological Examinations
Description	Number of participants with potentially clinically significant (PCS) vital signs and physical examinations are reported. Criteria for PCS vital signs include: respiratory rate >25 breaths/minute and PCS physical examinations include: an increase or decrease from baseline of >=7% in body weight.
Time Frame	Baseline up to end of treatment (Week 77)

Outcome Measure Data

Analysis Population Description

Safety population included all enrolled participants who received at least 1 dose of study treatment. Here "N" (Number of Participants Analyzed) represents number of participants who had at least 1 on-treatment assessment.

Arm/Group Title	Bosutinib
Arm/Group Description	Four bosutinib 100 milligram (mg) capsules, equivalent to 400 mg bosutinib orally once daily for 48 weeks, or until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Measure Participants	54
Respiratory Rate (> 25 breaths/minute)	6 8.2%
Weight (decrease >=7%)	9 12.3%
Weight (increase >=7%)	1 1.4%
Ophthalmological examinations	0 0%

9. Secondary Outcome

Title	Concomitant Medications Used for Management of Adverse Events (AEs)
Description	Number of participants taking any non-study medications which were administered from Study Day 1 to last dose of study treatment (Week 77) as a management of an AE were to be reported.
Time Frame	Day 1 up to end of treatment (Week 77)

Outcome Measure Data

Analysis Population Description

Data for this pre-specified outcome measure was not statistically summarized for analysis, but collected and reported in individual participant listings as planned.

Arm/Group Title	Bosutinib
Arm/Group Description	Four bosutinib 100 milligram (mg) capsules, equivalent to 400 mg bosutinib orally once daily for 48 weeks, or until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Measure Participants	0

10. Secondary Outcome

Title	Change From Baseline in Karnofsky Performance Status (KPS) at Week 1, 4, 8, 12, 16, Every 8 Weeks Thereafter and 14 Days After Last Dose of Study Treatment
Description	KPS: 11 level score ranged 100 to 0, to assess functional impairment. 100:Normal; 90:Able to carry on normal activity; 80:Normal activity with effort, some signs or symptoms of disease; 70:Cares for self, unable to carry on normal activity or to do active work; 60:Requires occasional assistance but is able to care for most of needs; 50:Requires considerable assistance and frequent medical care; 40:Disabled,requires special care and assistance; 30:Severely disabled; hospitalization indicated although death is not imminent; 20:Very sick; 10:Morbibund,fatal processes progressing rapidly; 0:Death.
Time Frame	Baseline, Weeks 1,4,8,12,16, every 8 weeks thereafter and 14 days after last dose of study treatment

Outcome Measure Data

Analysis Population Description

Data for this pre-specified outcome was collected but not statistically summarized for analysis as there were no clinically significant changes observed.

Arm/Group Title	Bosutinib
Arm/Group Description	Four bosutinib 100 milligram (mg) capsules, equivalent to 400 mg bosutinib orally once daily for 48 weeks, or until disease progression, unacceptable toxicity or withdrawal of consent occurred.
Measure Participants	0

11. Other Pre-specified Outcome

Title	Population Pharmacokinetics (PK)
Description	Data for this Outcome Measure are not reported here because the analysis population includes participants who were not enrolled in this study. ClinicalTrials.gov is designed for reporting results from only those participants who were enrolled in the study and described in the Participant Flow and Baseline Characteristics modules.
Time Frame	Pre-dose, 2, 7, 20 hours post-dose on Day 1 of Week 4 and pre-dose on Day 1 of Weeks 1, 8, 12, 16, and 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

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	Bosutinib
Arm/Group Description	Four bosutinib 100 milligram (mg) capsules, equivalent to 400 mg bosutinib orally once daily for 48 weeks, or until disease progression, unacceptable toxicity or withdrawal of consent occurred.
All Cause Mortality
	Bosutinib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Bosutinib
	Affected / at Risk (%)	# Events
Total	24/73 (32.9%)
Gastrointestinal disorders
Diarrhoea	2/73 (2.7%)
Ileus	1/73 (1.4%)
Vomiting	1/73 (1.4%)
General disorders
Disease progression	2/73 (2.7%)
Oedema peripheral	2/73 (2.7%)
Chest discomfort	1/73 (1.4%)
General physical health deterioration	1/73 (1.4%)
Performance status decreased	1/73 (1.4%)
Hepatobiliary disorders
Cytolytic hepatitis	1/73 (1.4%)
Hepatic failure	1/73 (1.4%)
Infections and infestations
Gastroenteritis	1/73 (1.4%)
Lower respiratory tract infection	1/73 (1.4%)
Investigations
Alanine aminotransferase increased	3/73 (4.1%)
Aspartate aminotransferase increased	2/73 (2.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/73 (1.4%)
Back pain	1/73 (1.4%)
Musculoskeletal pain	1/73 (1.4%)
Pathological fracture	1/73 (1.4%)
Nervous system disorders
Coma	1/73 (1.4%)
Psychiatric disorders
Confusional state	1/73 (1.4%)
Restlessness	1/73 (1.4%)
Reproductive system and breast disorders
Breast pain	2/73 (2.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	2/73 (2.7%)
Hydrothorax	1/73 (1.4%)
Other (Not Including Serious) Adverse Events
	Bosutinib
	Affected / at Risk (%)	# Events
Total	70/73 (95.9%)
Blood and lymphatic system disorders
Anaemia	4/73 (5.5%)
Gastrointestinal disorders
Diarrhoea	48/73 (65.8%)
Nausea	40/73 (54.8%)
Vomiting	33/73 (45.2%)
Abdominal pain	9/73 (12.3%)
Dyspepsia	7/73 (9.6%)
Abdominal pain upper	6/73 (8.2%)
Constipation	6/73 (8.2%)
General disorders
Fatigue	19/73 (26%)
Asthenia	14/73 (19.2%)
Pyrexia	7/73 (9.6%)
Oedema peripheral	6/73 (8.2%)
Investigations
Malaise	4/73 (5.5%)
Alanine aminotransferase increased	9/73 (12.3%)
Aspartate aminotransferase increased	9/73 (12.3%)
Weight decreased	8/73 (11%)
Metabolism and nutrition disorders
Anorexia	14/73 (19.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	9/73 (12.3%)
Back pain	9/73 (12.3%)
Myalgia	5/73 (6.8%)
Nervous system disorders
Headache	10/73 (13.7%)
Respiratory, thoracic and mediastinal disorders
Cough	8/73 (11%)
Dyspnoea	7/73 (9.6%)
Skin and subcutaneous tissue disorders
Rash	10/73 (13.7%)

Limitations/Caveats

[Not Specified]

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.