PF-00489791 For The Treatment Of Raynaud's

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01090492
• Collaborator: (none)
• Enrollment: 243
• Locations: 55
• Arms: 8
• Actual Duration (Months): 9.9
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The investigators propose that once daily administration of PF-00489791, a phosphodiesterase inhibitor, will reduce vasospasm and improve symptoms and signs associated with Primary and Secondary Raynaud's Phenomenon.

Condition or Disease	Intervention/Treatment	Phase
Raynaud's Disease; Peripheral Vascular Disease	Drug: PF-00489791; Drug: PF-00489791; Drug: PF-00489791; Drug: PF-00489791; Drug: PF-00489791; Drug: PF-00489791; Drug: PF-00489791; Drug: PF-00489791	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 243 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2a Randomized Double-blinded, Placebo And Active Controlled Two Cohort Two Doses Cross-over Multi-center Clinical Study To Assess Efficacy Of A Once Daily Administration Of A Phosphodiesterase 5 Inhibitor (Pf-00489791) For The Treatment Of Vasospasm In Primary And Secondary Raynaud's Phenomenon
• Actual Study Start Date: Aug 4, 2010
• Actual Primary Completion Date: May 31, 2011
• Actual Study Completion Date: May 31, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Secondary Raynaud 4 mg dose (period 1)	Drug: PF-00489791; Subjects with Secondary Raynaud's Phenomenon will receive PF-00489791 4 mg once a day for the first 4 week cross over period and then placebo once a day for the second 4 week cross over period
Experimental: Secondary Raynaud 4 mg dose (period 2)	Drug: PF-00489791; Subjects with Secondary Raynaud's Phenomenon will receive placebo once a day for the first 4 week cross over period and then PF-00489791 4 mg once a day for the second 4 week cross over period
Experimental: Secondary Raynaud 20 mg dose (period 1)	Drug: PF-00489791; Subjects with Secondary Raynaud's Phenomenon will receive PF-00489791 20 mg once a day for the first 4 week cross over period and then placebo once a day for the second 4 week cross over period
Experimental: Secondary Raynaud 20 mg dose (period 2)	Drug: PF-00489791; Subjects with Secondary Raynaud's Phenomenon will receive placebo once a day for the first 4 week cross over period and then PF-00489791 20 mg once a day for the second 4 week cross over period
Experimental: Primary Raynaud 4 mg dose (period 1)	Drug: PF-00489791; Subjects with Primary Raynaud's Phenomenon will receive PF-00489791 4 mg once a day for the first 4 week cross over period and then placebo once a day for the second 4 week cross over period
Experimental: Primary Raynaud 4 mg dose (period 2)	Drug: PF-00489791; Subjects with Primary Raynaud's Phenomenon will receive placebo once a day for the first 4 week cross over period and then PF-00489791 4 mg once a day for the second 4 week cross over period
Experimental: Primary Raynaud 20 mg dose (period 1)	Drug: PF-00489791; Subjects with Primary Raynaud's Phenomenon will receive PF-00489791 20 mg once a day for the first 4 week cross over period and then placebo once a day for the second 4 week cross over period
Experimental: Primary Raynaud 20 mg dose (period 2)	Drug: PF-00489791; Subjects with Primary Raynaud's Phenomenon will receive placebo once a day for the first 4 week cross over period and then PF-00489791 20 mg once a day for the second 4 week cross over period

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4 [Baseline, Week 4]

   The Raynaud's Condition score (RCS) is participant's rating of difficulty considering number of attacks, duration, amount of pain, numbness, or other symptoms caused in the fingers (including painful sores) due to the Raynaud's phenomenon every day and impact of Raynaud's alone on use of hands every day. An 11 point Likert scale is used to rate the difficulty caused by the condition each day with 0 = no difficulty and 10 = extreme difficulty. Participants were asked to select the number that best describes their difficulty, with higher score indicating worse condition. Average daily score was considered for participants completing more than 1 Raynaud's pain score scale on a day. Baseline value was calculated as mean of the scores over 7 days prior to treatment start. Week 4 value was calculated as mean of the scores over the 7-day period prior to Week 4.

Secondary Outcome Measures

1. Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4 [Baseline, Week 1, Week 2, Week 3, Week 4]

   Change from baseline in the number of Raynaud's attacks at Week 1, Week 2, Week 3 and Week 4 was calculated from the number of attacks reported over the 7-day period prior to each week from the patient diary, respectively.

2. Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4 [Baseline, Week 4]

   Mean duration of Raynaud's attacks for a time period was calculated as sum of recorded durations of attacks in the time period divided by total number of attacks in the time period where duration was recorded.

3. Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4 [Baseline, Week 1, 2, 3, 4]

   Participants were asked to rate their worst Raynaud's pain in the past 24 hours using an 11 point Likert scale, with 0 = no Raynaud's pain and 10 = the worst possible pain. Highest (most severe) response was considered for participants responding at more than 1 point on the scale. Average daily score was considered for participants completing more than 1 Raynaud's pain score scale on a day. Baseline value was calculated as mean of the scores over 7 days prior to treatment start. Post-baseline value was calculated as mean of the scores over the 7-day period prior to the visit.

4. Number of Participants With Decrease From Baseline in Digital Ulcers at Day 14 and 28: Secondary Raynaud's Phenomenon Cohort [Baseline, Day 14, 28]

   Presence of ulcer was assessed at baseline. At post-baseline visits, each ulcer was measured and scored: 1= smaller or improved compared to previous visit, 2= same as previous visit, 3= bigger or worse than previous visit, and 4= new. If a new digital ulcer develops during the course of the study, the measurement and scoring were initiated on this additional ulcer. Healed ulcers were not counted into the number of ulcers. Participants with SRP in the per-protocol population with at least 1 digital ulcer present at any assessment were evaluable for this measure. Results are reported for participants with presence of ulcer at baseline and decrease from baseline in ulcers at post-baseline visits.

5. Plasma Concentration of PF-00489791 and Its Metabolites [Day 1, 15, 29 (Day 1, 15, 29 for first intervention period), 43, 57, 71 (Day 1, 15, 29 for second intervention period)]

   Only participants receiving PF-00489791 were to be analyzed for this outcome. Data have been calculated by setting plasma concentration values below the lower limit of quantification to 0. The lower limit of quantification is 0.0100 microgram per milliliter (mcg/mL). Data for plasma concentration of PF-00489791 metabolites was not analyzed, as it was not intended to be a secondary endpoint and was deemed optional.

6. Number of Participants With Laboratory Test Abnormalities [Screening up to 28 days after last study dose (up to 98 days)]

   Criteria for laboratory tests abnormalities included: hemoglobin, hematocrit and red blood cells (less than [<] 0.8*lower limit of normal[LLN]); leukocytes (<0.6 LLN /greater than [>] 1.5*upper LN [ULN]; platelets (<0.5*LLN/>1.75*ULN); neutrophils, lymphocytes (<0.8* LLN/>1.2*ULN); eosinophils, basophils, monocytes (>1.2*ULN); bilirubin (>1.5*ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), Gamma GT, alkaline phosphatase (>3*ULN); BUN, creatinine (>1.3*ULN); glucose (<0.6 LLN/>1.5*ULN); uric acid (>1.2*ULN); sodium (<0.95*LLN/>1.05*ULN); potassium, calcium, chloride, bicarbonate (<0.9*LLN/>1.1*ULN); albumin, total protein (<0.8*LLN/>1.2*ULN); creatine kinase (>2.0*ULN); Urine Specific Gravity, Urine pH, urine blood, urine glucose, urine protein, urine ketones, urine leukocytes esterase (>=1 high-powered field). Total number of participants with any laboratory abnormalities was reported.

7. Number of Participants With Clinically Significant Changes in Vital Signs and Orthostatic Blood Pressure Measurements [Screening up to 28 days after last study dose (up to 98 days)]

   Vital signs assessment included measurement of supine and standing pulse rate, systolic and diastolic blood pressures. Criteria for clinically significant vital signs and orthostatic blood pressure measurements were based on investigator's judgement.

8. Number of Participants With Abnormal Electrocardiogram (ECG) Values [Screening up to 28 days after last study dose (up to 98 days)]

   ECG assessment included measurement of PR, QRS, QT,corrected QT interval (QTc)values. Criteria for clinically significant ECG values were based on investigator's judgement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Active Raynaud's Phenomenon

• Stable disease and medication requirements over the previous two months

• For Secondary Raynaud's Phenomenon subjects, a diagnosis of scleroderma using the American College of Rheumatology criteria or by the presence of at least 3/5 features of CREST syndrome

• both sexes

Exclusion Criteria:

• Uncontrolled hypertension, diabetes mellitus, angina, or using oral nitrates

• Smoking within 3 months or smoking cessation using nicotine products

• Subjects currently taking sildenafil, tadalafil or vardenafil

• Subjects with ulnar arterial occlusive disease as shown by a modified Allen test

• Pregnant or breast feeding or considering pregnancy in next 4 months

• Participation in trial for investigational drug within 30 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Hospital and Outpatient Center	Redwood City	California	United States	94063
2	University of Connecticut Health Center	Farmington	Connecticut	United States	06030-5353
3	Georgetown University Hospital	Washington	District of Columbia	United States	20007
4	Arthritis and Rheumatology of Georgia	Atlanta	Georgia	United States	30342
5	Rockford Orthopedic Associates	Rockford	Illinois	United States	61107
6	Diagnostic Rheumatology and Research, PC	Indianapolis	Indiana	United States	46227
7	Memorial Health System, Inc. dba Memorial Medical Group Clinical Research Institute	South Bend	Indiana	United States	46601
8	Johns Hopkins University - Division of Rheumatology	Baltimore	Maryland	United States	21224
9	The Center for Rheumatology and Bone Research	Wheaton	Maryland	United States	20902
10	Clinical Pharmacology Study Group	Worcester	Massachusetts	United States	01610
11	University of Michigan	Ann Arbor	Michigan	United States	48106
12	University of Michigan Health System	Ann Arbor	Michigan	United States	48109
13	West Michigan Rheumatology, PLLC	Grand Rapids	Michigan	United States	49546
14	Physician Research Collaboration, LLC	Lincoln	Nebraska	United States	68516
15	UMDNJ - Robert Wood Johnson Medical Center Clinical Research Center	New Brunswick	New Jersey	United States	08903-0019
16	The Center for Rheumatology	Albany	New York	United States	12206
17	Regional Rheumatology Associates	Binghamton	New York	United States	13905
18	AAIR Research Center	Rochester	New York	United States	14618
19	East Penn Rheumatology Associates, PC	Bethlehem	Pennsylvania	United States	18015
20	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
21	Rheumatic Disease Associates, Ltd.	Willow Grove	Pennsylvania	United States	19090
22	Metroplex Clinical Research Center	Dallas	Texas	United States	75231
23	Rainier Clinical Research Center, Inc.	Renton	Washington	United States	98057
24	Arthritis Centre Health Sciences Centre	Winnipeg	Manitoba	Canada	R3A 1M4
25	St. Joseph's Health Centre	London	Ontario	Canada	N6A 4V2
26	Rheumatology Research Associates	Ottawa	Ontario	Canada	K1H 1A2
27	Sir Mortimer B. Davis, Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2
28	Centro Integral de Reumatologia e Inmunologia CIREI	Bogota	Cundinamarca	Colombia	0000
29	Fundacion Instituto de Reumatologia Fernando Chalem	Bogota	Cundinamarca	Colombia	0000
30	Idearg Sas	Bogotá	Cundinamarca	Colombia	0000
31	Servimed E.U	Bucaramanga	Santander	Colombia	0000
32	Medicity S.A.S	Bucaramanga		Colombia	0000
33	REVMATOLOGIE s.r.o.,	Brno		Czechia	638 00
34	Fakultni nemocnice Hradec Kralove	Hradec Kralove		Czechia	500 05
35	Revmatologicky ustav	Praha 2		Czechia	128 50
36	Dermatologisches Ambulatorium Hamburg-Alstertal	Hamburg		Germany	22391
37	Semmelweis Egyetem, Ersebeszeti Klinika	Budapest		Hungary	1122
38	Bacs-Kiskun Megyei Onkormanyzat Korhaza Szegedi Tudomanyegyetem AOK Oktato Korhaza	Kecskemet		Hungary	6000
39	Vas Megyei Markusovszky Korhaz Nonprofit Zrt, Angiologiai Szakambulancia	Szombathely		Hungary	9700
40	Seoul National University Hospital, Rheumatology, Internal Medicine	Seoul		Korea, Republic of	110-744
41	Yonsei University College of Medicine, Severance Hospital, Rheumatology, Internal Medicine	Seoul		Korea, Republic of	120-752
42	The Catholic University of Korea, Seoul St. Mary's Hospital/ Rheumatology, Internal Medicine	Seoul		Korea, Republic of	137-701
43	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Mexico	DF	Mexico	14000
44	Unidad de Investigacion en Enfermedades Cronico Degenerativas	Guadalajara	Jalisco	Mexico	44620
45	Hospital Angeles. Centro Medico del Potosi	San Luis Potosi		Mexico	78200
46	Slaskie Centrum Osteoporozy	Katowice		Poland	40-084
47	Prywatna Praktyka Lekarska Dr Med. Pawel Hrycaj	Poznan		Poland	61-397
48	Prywatna Praktyka Lekarska Prof. UM Dr hab. med. Pawel Hrycaj	Poznan		Poland	61-397
49	Katedra i Klinika Dermatologii, Wenerologii i Alergologii Akademii Medycznej we Wroclawiu	Wroclaw		Poland	50-368
50	Hospital Clinico Universitario Santiago de Compostela	Santiago de Compostela	A Coruña	Spain	15706
51	Hospital Del Mar	Barcelona		Spain	08003
52	Hospital Universitario 12 de Octubre	Madrid		Spain	28041
53	CTC, Centrum för klinisk provning, Sahlgrenska Universitetssjukhuset	Goteborg		Sweden	413 45
54	Reumatologkliniken Skanes Universitetssjukhus Lund	Lund		Sweden	221 85
55	Karolinska Universitetssjukhuset Solna, Reumatologiska kliniken	Stockholm		Sweden	171 76

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: NCT01090492
• Other Study ID Numbers: A7331010; EudraCT 2010-019009-40; 2010-019009-40
• First Posted: Mar 22, 2010
• Last Update Posted: May 16, 2018
• Last Verified: Apr 1, 2018

• Keywords provided by Pfizer: Raynaud's phenomenon; vasospasm; scleroderma; systemic sclerosis; CREST; phosphodiesterase inhibitor
• Additional relevant MeSH terms: Vascular Diseases; Peripheral Vascular Diseases; Peripheral Arterial Disease; Raynaud Disease

Study Results

Participant Flow

Pre-assignment Detail	A total of 243 participants were stratified into 2 cohorts (Primary Raynaud's phenomenon[PRP] and secondary RP[SRP]), who entered a 2-week placebo run-in period (to establish baseline), followed by a cross-over period (first 4 week treatment period,then a 2 week placebo washout,then 4 week treatment period) and then a 2-week placebo run-out period.

Arm/Group Title	PRP Cohort: Placebo First, Then PF-00489791 4 mg	PRP Cohort: PF-00489791 4mg First, Then Placebo	PRP Cohort: Placebo First, Then PF-00489791 20 mg	PRP Cohort: PF-00489791 20 mg First, Then Placebo	SRP Cohort: Placebo First, Then PF-00489791 4 mg	SRP Cohort: PF-00489791 4 mg First, Then Placebo	SRP Cohort: Placebo First, Then PF-00489791 20 mg	SRP Cohort: PF-00489791 20 mg First, Then Placebo
Arm/Group Description	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first intervention period and then PF-00489791 tablets 4 milligram (mg) (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in second intervention period to participants with PRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily.	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first intervention period and then 2 placebo tablets matched to PF-00489791 orally once daily for 4 weeks in second intervention period to participants with PRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first intervention period and then PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in second intervention period to participants with PRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first intervention period and then 2 placebo tablets matched to PF-00489791 orally once daily for 4 weeks in second intervention period to participants with PRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first intervention period and then PF-00489791 tablets 4 milligram (mg) (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in second intervention period to participants with SRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily.	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first intervention period and then 2 placebo tablets matched to PF-00489791 orally once daily for 4 weeks in second intervention period to participants with SRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first intervention period and then PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in second intervention period to participants with SRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first intervention period and then 2 placebo tablets matched to PF-00489791 orally once daily for 4 weeks in second intervention period to participants with SRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily.
Period Title: First Intervention Period (4 Weeks)
STARTED	27	29	29	28	33	32	32	33
COMPLETED	26	24	26	22	29	30	31	27
NOT COMPLETED	1	5	3	6	4	2	1	6
Period Title: First Intervention Period (4 Weeks)
STARTED	26	24	26	22	29	30	31	27
COMPLETED	26	24	26	22	29	30	31	27
NOT COMPLETED	0	0	0	0	0	0	0	0
Period Title: First Intervention Period (4 Weeks)
STARTED	26	24	26	22	29	30	31	27
COMPLETED	25	22	24	22	27	29	22	25
NOT COMPLETED	1	2	2	0	2	1	9	2

Baseline Characteristics

Arm/Group Title	PRP Cohort: Placebo First, Then PF-00489791 4 mg	PRP Cohort: PF-00489791 4mg First, Then Placebo	PRP Cohort: Placebo First, Then PF-00489791 20 mg	PRP Cohort: PF-00489791 20 mg First, Then Placebo	SRP Cohort: Placebo First, Then PF-00489791 4 mg	SRP Cohort: PF-00489791 4 mg First, Then Placebo	SRP Cohort: Placebo First, Then PF-00489791 20 mg	SRP Cohort: PF-00489791 20 mg First, Then Placebo	Total
Arm/Group Description	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first intervention period and then PF-00489791 tablets 4 milligram (mg) (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in second intervention period to participants with PRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily.	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first intervention DB period and 2 placebo tablets matched to PF-00489791 orally once daily for 4 weeks in second DB intervention period to participants with PRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first intervention period and then PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in second DB intervention period to participants with PRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first intervention period and then 2 placebo tablets matched to PF-00489791 orally once daily for 4 weeks in second intervention period to participants with PRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first intervention period and then PF-00489791 tablets 4 milligram (mg) (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in second intervention period to participants with SRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily.	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first intervention period and then 2 placebo tablets matched to PF-00489791 orally once daily for 4 weeks in second intervention period to participants with SRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first intervention period and then PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in second intervention period to participants with SRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first intervention period and then 2 placebo tablets matched to PF-00489791 orally once daily for 4 weeks in second intervention period to participants with SRP. A washout period of 2 weeks was maintained between each intervention period during which 2 placebo tablets matched to PF-00489791 were given orally once daily.	Total of all reporting groups
Overall Participants	27	29	29	28	33	32	32	33	243
Age, Customized (Count of Participants)
Between 18 to 44 years	14 51.9%	12 41.4%	14 48.3%	14 50%	10 30.3%	6 18.8%	16 50%	9 27.3%	95 39.1%
Between 45 to 64 years	13 48.1%	16 55.2%	15 51.7%	14 50%	22 66.7%	26 81.3%	16 50%	24 72.7%	146 60.1%
Greater than or equal to (>=) 65 years	0 0%	1 3.4%	0 0%	0 0%	1 3%	0 0%	0 0%	0 0%	2 0.8%
Sex: Female, Male (Count of Participants)
Female	25 92.6%	25 86.2%	25 86.2%	26 92.9%	30 90.9%	30 93.8%	31 96.9%	28 84.8%	220 90.5%
Male	2 7.4%	4 13.8%	4 13.8%	2 7.1%	3 9.1%	2 6.3%	1 3.1%	5 15.2%	23 9.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Mean Raynaud's Condition Score (RCS) at Week 4
Description	The Raynaud's Condition score (RCS) is participant's rating of difficulty considering number of attacks, duration, amount of pain, numbness, or other symptoms caused in the fingers (including painful sores) due to the Raynaud's phenomenon every day and impact of Raynaud's alone on use of hands every day. An 11 point Likert scale is used to rate the difficulty caused by the condition each day with 0 = no difficulty and 10 = extreme difficulty. Participants were asked to select the number that best describes their difficulty, with higher score indicating worse condition. Average daily score was considered for participants completing more than 1 Raynaud's pain score scale on a day. Baseline value was calculated as mean of the scores over 7 days prior to treatment start. Week 4 value was calculated as mean of the scores over the 7-day period prior to Week 4.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description

Per-protocol analysis set (PPAS) included all randomized participants compliant with diary completion and were not amongst serious protocol violators, receiving study medication till the study completion.

Arm/Group Title	PF-00489791 4 mg (PRP)	PF-00489791 20 mg (PRP)	Placebo (PRP)	PF-00489791 4 mg (SRP)	PF-00489791 20 mg (SRP)	Placebo (SRP)
Arm/Group Description	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with PRP.	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with SRP.
Measure Participants	34	39	73	47	36	83
Baseline	3.04 (1.899)	2.90 (2.160)	2.98 (1.958)	3.14 (2.431)	2.53 (1.833)	2.97 (2.492)
Change at Week 4	-0.76 (1.901)	-1.05 (1.771)	-0.61 (1.404)	-0.82 (1.624)	-0.15 (1.090)	-0.24 (1.437)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-00489791 4 mg (PRP), Placebo (PRP)
	Comments	PRP: Adjusted mean difference analysis was based on Analysis of Covariance (ANCOVA) model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6513
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 80%; -0.21 to 0.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-00489791 20 mg (PRP), Placebo (PRP)
	Comments	PRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0057
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-0.69
	Confidence Interval	(2-Sided) 80%; -0.99 to -0.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-00489791 4 mg (SRP), Placebo (SRP)
	Comments	SRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1157
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-0.44
	Confidence Interval	(2-Sided) 80%; -0.80 to -0.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-00489791 20 mg (SRP), Placebo (SRP)
	Comments	SRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6286
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 80%; -0.56 to 0.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in the Number of Raynaud's Attacks at Week 1, 2, 3 and 4
Description	Change from baseline in the number of Raynaud's attacks at Week 1, Week 2, Week 3 and Week 4 was calculated from the number of attacks reported over the 7-day period prior to each week from the patient diary, respectively.
Time Frame	Baseline, Week 1, Week 2, Week 3, Week 4

Outcome Measure Data

Analysis Population Description

PPAS included all randomized participants compliant with diary completion and were not amongst serious protocol violators, receiving study medication till the study completion. Here, number analyzed signifies those participants who were evaluable at specified time points.

Arm/Group Title	PF-00489791 4 mg (PRP)	PF-00489791 20 mg (PRP)	Placebo (PRP)	PF-00489791 4 mg (SRP)	PF-00489791 20 mg (SRP)	Placebo (SRP)
Arm/Group Description	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with PRP.	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with SRP.
Measure Participants	34	39	73	47	36	83
Baseline	22.06 (20.587)	16.31 (10.885)	20.19 (17.802)	22.80 (16.270)	23.70 (20.909)	23.08 (20.698)
Change at Week 1	-3.75 (7.494)	-2.47 (6.477)	-1.41 (7.934)	-3.17 (7.994)	-4.49 (14.692)	-2.36 (11.850)
Change at Week 2	-5.30 (9.487)	-2.36 (8.371)	-2.45 (11.107)	-3.76 (9.028)	-4.43 (17.312)	-1.87 (11.051)
Change at Week 3	-4.66 (10.559)	-4.86 (5.681)	-4.03 (10.396)	-4.25 (11.408)	-3.75 (8.601)	-1.93 (9.487)
Change at Week 4	-4.85 (13.008)	-3.07 (7.118)	-3.65 (10.460)	-3.89 (8.326)	-2.68 (10.002)	-2.25 (10.624)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-00489791 4 mg (PRP), Placebo (PRP)
	Comments	At Week 4 - PRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9504
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 80%; -2.43 to 2.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-00489791 20 mg (PRP), Placebo (PRP)
	Comments	At Week 4 - PRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4651
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-1.35
	Confidence Interval	(2-Sided) 80%; -3.74 to 1.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-00489791 4 mg (SRP), Placebo (SRP)
	Comments	At Week 4 - SRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7423
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 80%; -2.92 to 1.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-00489791 20 mg (SRP), Placebo (SRP)
	Comments	At Week 4 - SRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3524
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-1.91
	Confidence Interval	(2-Sided) 80%; -4.55 to 0.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Mean Duration of Raynaud's Attacks at Week 4
Description	Mean duration of Raynaud's attacks for a time period was calculated as sum of recorded durations of attacks in the time period divided by total number of attacks in the time period where duration was recorded.
Time Frame	Baseline, Week 4

Outcome Measure Data

Analysis Population Description

PPAS included all randomized participants compliant with diary completion and were not amongst serious protocol violators, receiving study medication till the study completion. Here, number analyzed signifies those participants who were evaluable at specified time points.

Arm/Group Title	PF-00489791 4 mg (PRP)	PF-00489791 20 mg (PRP)	Placebo (PRP)	PF-00489791 4 mg (SRP)	PF-00489791 20 mg (SRP)	Placebo (SRP)
Arm/Group Description	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with PRP.	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with SRP.
Measure Participants	34	39	73	47	36	83
Baseline	17.69 (13.184)	22.23 (36.562)	19.61 (40.603)	19.37 (18.929)	19.07 (18.196)	19.91 (19.886)
Change at Week 4	-2.89 (7.480)	-5.63 (43.067)	-1.41 (12.348)	-3.92 (11.336)	-2.61 (9.593)	-1.65 (10.609)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-00489791 4 mg (PRP), Placebo (PRP)
	Comments	PRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7900
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 80%; -4.61 to 7.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-00489791 20 mg (PRP), Placebo (PRP)
	Comments	PRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1463
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-6.17
	Confidence Interval	(2-Sided) 80%; -11.61 to -0.73
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-00489791 4 mg (SRP), Placebo (SRP)
	Comments	SRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1446
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-2.37
	Confidence Interval	(2-Sided) 80%; -4.44 to -0.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-00489791 20 mg (SRP), Placebo (SRP)
	Comments	SRP: Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5497
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-1.09
	Confidence Interval	(2-Sided) 80%; -3.45 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in the Mean Raynaud's Pain Score at Week 1, 2, 3 and 4
Description	Participants were asked to rate their worst Raynaud's pain in the past 24 hours using an 11 point Likert scale, with 0 = no Raynaud's pain and 10 = the worst possible pain. Highest (most severe) response was considered for participants responding at more than 1 point on the scale. Average daily score was considered for participants completing more than 1 Raynaud's pain score scale on a day. Baseline value was calculated as mean of the scores over 7 days prior to treatment start. Post-baseline value was calculated as mean of the scores over the 7-day period prior to the visit.
Time Frame	Baseline, Week 1, 2, 3, 4

Outcome Measure Data

Analysis Population Description

PPAS included all randomized participants compliant with diary completion and were not amongst serious protocol violators, receiving study medication till the study completion. Here, number analyzed signifies those participants who were evaluable at specified time points.

Arm/Group Title	PF-00489791 4 mg (PRP)	PF-00489791 20 mg (PRP)	Placebo (PRP)	PF-00489791 4 mg (SRP)	PF-00489791 20 mg (SRP)	Placebo (SRP)
Arm/Group Description	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with PRP.	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with SRP.
Measure Participants	34	39	73	47	36	83
Baseline	2.84 (2.074)	2.78 (2.348)	2.80 (2.064)	3.33 (2.614)	2.54 (1.895)	3.10 (2.753)
Change at Week 1	-0.72 (1.525)	-0.74 (1.266)	-0.26 (1.205)	-0.53 (1.440)	-0.32 (1.276)	-0.17 (1.272)
Change at Week 2	-0.94 (1.745)	-0.61 (1.524)	-0.48 (1.337)	-0.68 (1.740)	-0.33 (1.321)	-0.24 (1.306)
Change at Week 3	-0.82 (1.720)	-1.12 (1.664)	-0.62 (1.262)	-0.80 (1.836)	-0.55 (1.081)	-0.33 (1.269)
Change at Week 4	-0.80 (1.842)	-1.14 (1.820)	-0.63 (1.423)	-0.77 (1.922)	-0.35 (1.115)	-0.27 (1.466)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-00489791 4 mg (PRP), Placebo (PRP)
	Comments	Week 4 (PRP): Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5909
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	0.15
	Confidence Interval	(2-Sided) 80%; -0.21 to 0.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-00489791 20 mg (PRP), Placebo (PRP)
	Comments	Week 4 (PRP): Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0053
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-0.77
	Confidence Interval	(2-Sided) 80%; -1.12 to -0.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-00489791 4 mg (SRP), Placebo (SRP)
	Comments	Week 4 (SRP): Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3462
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 80%; -0.67 to 0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-00489791 20 mg (SRP), Placebo (SRP)
	Comments	Week 4 (SRP): Adjusted mean difference analysis was based on ANCOVA model with sequence, period and treatment as fixed effects and participant within sequence as a random effect, utilizing the baseline scores as covariate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1940
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Adjusted Mean Difference
	Estimated Value	-0.44
	Confidence Interval	(2-Sided) 80%; -0.88 to -0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Participants With Decrease From Baseline in Digital Ulcers at Day 14 and 28: Secondary Raynaud's Phenomenon Cohort
Description	Presence of ulcer was assessed at baseline. At post-baseline visits, each ulcer was measured and scored: 1= smaller or improved compared to previous visit, 2= same as previous visit, 3= bigger or worse than previous visit, and 4= new. If a new digital ulcer develops during the course of the study, the measurement and scoring were initiated on this additional ulcer. Healed ulcers were not counted into the number of ulcers. Participants with SRP in the per-protocol population with at least 1 digital ulcer present at any assessment were evaluable for this measure. Results are reported for participants with presence of ulcer at baseline and decrease from baseline in ulcers at post-baseline visits.
Time Frame	Baseline, Day 14, 28

Outcome Measure Data

Analysis Population Description

PPAS included all randomized participants compliant with diary completion and were not amongst serious protocol violators, receiving study medication till the study completion. Here, number analyzed signifies those participants who were evaluable at specified time points.

Arm/Group Title	PF-00489791 4 mg (SRP)	PF-00489791 20 mg (SRP)	Placebo (SRP)
Arm/Group Description	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with SRP.
Measure Participants	47	36	83
Baseline	10 37%	7 24.1%	16 55.2%
With Decrease at Day 14	7 25.9%	1 3.4%	6 20.7%
With Decrease at Day 28	9 33.3%	5 17.2%	7 24.1%

6. Secondary Outcome

Title	Plasma Concentration of PF-00489791 and Its Metabolites
Description	Only participants receiving PF-00489791 were to be analyzed for this outcome. Data have been calculated by setting plasma concentration values below the lower limit of quantification to 0. The lower limit of quantification is 0.0100 microgram per milliliter (mcg/mL). Data for plasma concentration of PF-00489791 metabolites was not analyzed, as it was not intended to be a secondary endpoint and was deemed optional.
Time Frame	Day 1, 15, 29 (Day 1, 15, 29 for first intervention period), 43, 57, 71 (Day 1, 15, 29 for second intervention period)

Outcome Measure Data

Analysis Population Description

Analysis population included participants who received 1 dose of study drug and were analyzed for pharmacokinetic parameters. Here, Overall number of participants signifies participants evaluable for either first or second intervention period and number analyzed signifies those participants who were evaluable at specified time points.

Arm/Group Title	PF-00489791 4 mg (PRP)	PF-00489791 20 mg (PRP)	PF-00489791 4 mg (SRP)	PF-00489791 20 mg (SRP)
Arm/Group Description	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.
Measure Participants	55	54	61	64
Day 1	0.0058 (0.0314)	NA (NA)	NA (NA)	NA (NA)
Day 15	0.1523 (0.0855)	0.5907 (0.3736)	0.1756 (0.09038)	0.7718 (0.4991)
Day 29	0.1489 (0.0854)	0.6525 (0.3822)	0.1776 (0.08508)	0.7577 (0.4137)
Day 43	NA (NA)	NA (NA)	NA (NA)	NA (NA)
Day 57	0.1088 (0.0629)	0.6890 (0.4318)	0.1167 (0.05644)	0.7565 (0.6224)
Day 71	0.1178 (0.0614)	0.6337 (0.3745)	0.1224 (0.0638)	0.6639 (0.5834)

7. Secondary Outcome

Title	Number of Participants With Laboratory Test Abnormalities
Description	Criteria for laboratory tests abnormalities included: hemoglobin, hematocrit and red blood cells (less than [<] 0.8*lower limit of normal[LLN]); leukocytes (<0.6 LLN /greater than [>] 1.5*upper LN [ULN]; platelets (<0.5*LLN/>1.75*ULN); neutrophils, lymphocytes (<0.8* LLN/>1.2*ULN); eosinophils, basophils, monocytes (>1.2*ULN); bilirubin (>1.5*ULN); aspartate aminotransferase (AST), alanine aminotransferase (ALT), Gamma GT, alkaline phosphatase (>3*ULN); BUN, creatinine (>1.3*ULN); glucose (<0.6 LLN/>1.5*ULN); uric acid (>1.2*ULN); sodium (<0.95*LLN/>1.05*ULN); potassium, calcium, chloride, bicarbonate (<0.9*LLN/>1.1*ULN); albumin, total protein (<0.8*LLN/>1.2*ULN); creatine kinase (>2.0*ULN); Urine Specific Gravity, Urine pH, urine blood, urine glucose, urine protein, urine ketones, urine leukocytes esterase (>=1 high-powered field). Total number of participants with any laboratory abnormalities was reported.
Time Frame	Screening up to 28 days after last study dose (up to 98 days)

Outcome Measure Data

Analysis Population Description

Analysis population included all randomized participants who took at least 1 dose of study medication along with at least 1 on-treatment laboratory test result.

Arm/Group Title	PF-00489791 4 mg (PRP)	PF-00489791 20 mg (PRP)	Placebo (PRP)	PF-00489791 4 mg (SRP)	PF-00489791 20 mg (SRP)	Placebo (SRP)
Arm/Group Description	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with PRP.	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with SRP.
Measure Participants	50	48	98	57	60	114
Number [participants]	2 7.4%	4 13.8%	14 48.3%	5 17.9%	13 39.4%	10 31.3%

8. Secondary Outcome

Title	Number of Participants With Clinically Significant Changes in Vital Signs and Orthostatic Blood Pressure Measurements
Description	Vital signs assessment included measurement of supine and standing pulse rate, systolic and diastolic blood pressures. Criteria for clinically significant vital signs and orthostatic blood pressure measurements were based on investigator's judgement.
Time Frame	Screening up to 28 days after last study dose (up to 98 days)

Outcome Measure Data

Analysis Population Description

Safety analysis set consisted of all participants who took at least 1 dose of study medication.

Arm/Group Title	PF-00489791 4 mg (PRP)	PF-00489791 20 mg (PRP)	Placebo (PRP)	PF-00489791 4 mg (SRP)	PF-00489791 20 mg (SRP)	Placebo (SRP)
Arm/Group Description	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with PRP.	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with SRP.
Measure Participants	55	54	102	61	64	122
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

9. Secondary Outcome

Title	Number of Participants With Abnormal Electrocardiogram (ECG) Values
Description	ECG assessment included measurement of PR, QRS, QT,corrected QT interval (QTc)values. Criteria for clinically significant ECG values were based on investigator's judgement.
Time Frame	Screening up to 28 days after last study dose (up to 98 days)

Outcome Measure Data

Analysis Population Description

Safety analysis set consisted of all participants who took at least 1 dose of study medication.

Arm/Group Title	PF-00489791 4 mg (PRP)	PF-00489791 20 mg (PRP)	Placebo (PRP)	PF-00489791 4 mg (SRP)	PF-00489791 20 mg (SRP)	Placebo (SRP)
Arm/Group Description	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with PRP.	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.	Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with SRP.
Measure Participants	55	54	102	61	64	122
Number [participants]	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Adverse Events

Adverse Event Reporting Description	Safety analysis population included all participants who received at least 1 dose of study medication.
Arm/Group Title	PF-00489791 4 mg (PRP)		PF-00489791 20 mg (PRP)		Placebo (PRP)		PF-00489791 4 mg (SRP)		PF-00489791 20 mg (SRP)		Placebo (SRP)
Arm/Group Description	PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.		PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with PRP.		Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with PRP.		PF-00489791 tablets 4 mg (2 tablets of PF-00489791 2 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.		PF-00489791 tablets 20 mg (2 tablets of PF-00489791 10 mg) orally once daily for 4 weeks in first or second intervention period to participants with SRP.		Two placebo tablets matched to PF-00489791 orally once daily for 4 weeks in first or second intervention period to participants with SRP.
All Cause Mortality
	PF-00489791 4 mg (PRP)		PF-00489791 20 mg (PRP)		Placebo (PRP)		PF-00489791 4 mg (SRP)		PF-00489791 20 mg (SRP)		Placebo (SRP)
	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	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Serious Adverse Events
	PF-00489791 4 mg (PRP)		PF-00489791 20 mg (PRP)		Placebo (PRP)		PF-00489791 4 mg (SRP)		PF-00489791 20 mg (SRP)		Placebo (SRP)
	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	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal adenocarcinoma	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Other (Not Including Serious) Adverse Events
	PF-00489791 4 mg (PRP)		PF-00489791 20 mg (PRP)		Placebo (PRP)		PF-00489791 4 mg (SRP)		PF-00489791 20 mg (SRP)		Placebo (SRP)
	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	27/55 (49.1%)		34/54 (63%)		43/102 (42.2%)		34/61 (55.7%)		51/64 (79.7%)		60/122 (49.2%)
Blood and lymphatic system disorders
Anaemia	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Leukopenia	0/55 (0%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Lymphadenopathy	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Neutropenia	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Cardiac disorders
Bradycardia	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Palpitations	1/55 (1.8%)		0/54 (0%)		2/102 (2%)		2/61 (3.3%)		1/64 (1.6%)		0/122 (0%)
Tachycardia	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		4/64 (6.3%)		0/122 (0%)
Congenital, familial and genetic disorders
Cystic fibrosis	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Ear and labyrinth disorders
Ear pain	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Tinnitus	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		3/122 (2.5%)
Vertigo	0/55 (0%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Eye disorders
Conjunctivitis	0/55 (0%)		0/54 (0%)		1/102 (1%)		1/61 (1.6%)		1/64 (1.6%)		0/122 (0%)
Dry eye	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		1/64 (1.6%)		0/122 (0%)
Eye discharge	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Eye oedema	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Eye pruritus	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		2/122 (1.6%)
Eyelid oedema	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Lacrimation increased	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Ocular hyperaemia	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Periorbital oedema	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Photophobia	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Vision blurred	0/55 (0%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		1/64 (1.6%)		1/122 (0.8%)
Gastrointestinal disorders
Abdominal discomfort	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		1/64 (1.6%)		0/122 (0%)
Abdominal distension	0/55 (0%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Abdominal pain	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Abdominal pain upper	2/55 (3.6%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Diarrhoea	2/55 (3.6%)		0/54 (0%)		4/102 (3.9%)		0/61 (0%)		7/64 (10.9%)		0/122 (0%)
Dry mouth	0/55 (0%)		0/54 (0%)		2/102 (2%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Dyspepsia	1/55 (1.8%)		5/54 (9.3%)		0/102 (0%)		2/61 (3.3%)		0/64 (0%)		1/122 (0.8%)
Dysphagia	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		1/122 (0.8%)
Flatulence	0/55 (0%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Gastritis	1/55 (1.8%)		0/54 (0%)		1/102 (1%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Gastrooesophageal reflux disease	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		1/61 (1.6%)		1/64 (1.6%)		0/122 (0%)
Gingivitis	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Nausea	5/55 (9.1%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		3/64 (4.7%)		2/122 (1.6%)
Oesophageal pain	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Oesophagitis	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Salivary gland calculus	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Stomatitis	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Toothache	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		1/122 (0.8%)
Vomiting	2/55 (3.6%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		2/64 (3.1%)		3/122 (2.5%)
General disorders
Adverse drug reaction	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Asthenia	0/55 (0%)		2/54 (3.7%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Chest pain	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		2/64 (3.1%)		1/122 (0.8%)
Face oedema	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Fatigue	1/55 (1.8%)		0/54 (0%)		3/102 (2.9%)		1/61 (1.6%)		1/64 (1.6%)		2/122 (1.6%)
Feeling hot	0/55 (0%)		0/54 (0%)		3/102 (2.9%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Inflammation	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Influenza like illness	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Malaise	1/55 (1.8%)		1/54 (1.9%)		1/102 (1%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Oedema	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		3/64 (4.7%)		0/122 (0%)
Oedema peripheral	0/55 (0%)		2/54 (3.7%)		2/102 (2%)		3/61 (4.9%)		3/64 (4.7%)		0/122 (0%)
Pain	1/55 (1.8%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Pyrexia	1/55 (1.8%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Ulcer	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Immune system disorders
Hypersensitivity	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Seasonal allergy	0/55 (0%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Infections and infestations
Alveolar osteitis	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Bacteriuria	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Bronchitis	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		1/122 (0.8%)
Cystitis	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Furuncle	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Gastroenteritis viral	1/55 (1.8%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Gastrointestinal infection	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Influenza	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		4/122 (3.3%)
Laryngitis	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Localised infection	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Nasopharyngitis	3/55 (5.5%)		2/54 (3.7%)		3/102 (2.9%)		1/61 (1.6%)		3/64 (4.7%)		4/122 (3.3%)
Oesophageal candidiasis	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Oral herpes	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Otitis externa	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Otitis media	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Pharyngotonsillitis	0/55 (0%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Rash pustular	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Respiratory tract infection	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		1/122 (0.8%)
Sialoadenitis	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Sinusitis	2/55 (3.6%)		1/54 (1.9%)		2/102 (2%)		0/61 (0%)		2/64 (3.1%)		2/122 (1.6%)
Tonsillitis	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Tooth abscess	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Tooth infection	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		2/122 (1.6%)
Upper respiratory tract infection	0/55 (0%)		0/54 (0%)		10/102 (9.8%)		2/61 (3.3%)		1/64 (1.6%)		5/122 (4.1%)
Urinary tract infection	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Vaginitis bacterial	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Viral infection	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Injury, poisoning and procedural complications
Fall	0/55 (0%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Frostbite	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Laceration	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Limb injury	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Thermal burn	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Investigations
Alanine aminotransferase increased	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Blood creatine phosphokinase increased	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Blood potassium increased	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Blood pressure increased	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Electrocardiogram abnormal	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Gamma-glutamyltransferase increased	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Haemoglobin decreased	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Heart rate increased	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Transaminases increased	0/55 (0%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Weight increased	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Metabolism and nutrition disorders
Decreased appetite	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Fluid retention	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		1/122 (0.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/55 (1.8%)		2/54 (3.7%)		0/102 (0%)		2/61 (3.3%)		1/64 (1.6%)		0/122 (0%)
Back pain	0/55 (0%)		2/54 (3.7%)		1/102 (1%)		2/61 (3.3%)		5/64 (7.8%)		0/122 (0%)
Fibromyalgia	0/55 (0%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Joint swelling	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Muscle spasms	1/55 (1.8%)		1/54 (1.9%)		0/102 (0%)		2/61 (3.3%)		0/64 (0%)		2/122 (1.6%)
Musculoskeletal pain	0/55 (0%)		0/54 (0%)		2/102 (2%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Musculoskeletal stiffness	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Myalgia	2/55 (3.6%)		3/54 (5.6%)		1/102 (1%)		4/61 (6.6%)		7/64 (10.9%)		3/122 (2.5%)
Neck pain	0/55 (0%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Pain in extremity	2/55 (3.6%)		3/54 (5.6%)		2/102 (2%)		0/61 (0%)		2/64 (3.1%)		1/122 (0.8%)
Pain in jaw	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Polyarthritis	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Sensation of heaviness	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Synovitis	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Tendonitis	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of cornea	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Nervous system disorders
Balance disorder	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Dizziness	1/55 (1.8%)		1/54 (1.9%)		1/102 (1%)		3/61 (4.9%)		3/64 (4.7%)		4/122 (3.3%)
Headache	8/55 (14.5%)		14/54 (25.9%)		9/102 (8.8%)		9/61 (14.8%)		21/64 (32.8%)		12/122 (9.8%)
Hypoaesthesia	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Migraine	0/55 (0%)		1/54 (1.9%)		1/102 (1%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Paraesthesia	0/55 (0%)		1/54 (1.9%)		1/102 (1%)		1/61 (1.6%)		1/64 (1.6%)		0/122 (0%)
Parosmia	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Sciatica	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Sinus headache	0/55 (0%)		0/54 (0%)		2/102 (2%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Syncope	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Tremor	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Psychiatric disorders
Anxiety	0/55 (0%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Depression	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		1/64 (1.6%)		1/122 (0.8%)
Insomnia	0/55 (0%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Mood swings	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Orgasm abnormal	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Renal and urinary disorders
Proteinuria	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Renal impairment	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Urinary incontinence	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Reproductive system and breast disorders
Erection increased	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		1/64 (1.6%)		0/122 (0%)
Menstruation irregular	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Metrorrhagia	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Nipple pain	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Spontaneous penile erection	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		2/64 (3.1%)		0/122 (0%)
Vaginal haemorrhage	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Respiratory, thoracic and mediastinal disorders
Allergic bronchitis	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Cough	1/55 (1.8%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		1/64 (1.6%)		2/122 (1.6%)
Dysphonia	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Dyspnoea	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Epistaxis	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		2/64 (3.1%)		0/122 (0%)
Nasal congestion	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Nasal obstruction	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Nasal ulcer	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Oropharyngeal pain	1/55 (1.8%)		2/54 (3.7%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		2/122 (1.6%)
Pleuritic pain	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Productive cough	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		1/122 (0.8%)
Respiratory disorder	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Rhinorrhoea	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		1/61 (1.6%)		1/64 (1.6%)		0/122 (0%)
Sinus congestion	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Vasomotor rhinitis	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Wheezing	0/55 (0%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Skin and subcutaneous tissue disorders
Acne	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Acne cystic	0/55 (0%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Alopecia	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Dry skin	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		1/64 (1.6%)		0/122 (0%)
Eczema	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		2/64 (3.1%)		0/122 (0%)
Erythema	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		2/64 (3.1%)		0/122 (0%)
Increased tendency to bruise	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Nail bed inflammation	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Pain of skin	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Pruritus	0/55 (0%)		0/54 (0%)		1/102 (1%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Rash	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Rash erythematous	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		1/122 (0.8%)
Rash pruritic	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Skin burning sensation	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Skin disorder	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Skin lesion	0/55 (0%)		0/54 (0%)		1/102 (1%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Skin ulcer	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		1/64 (1.6%)		0/122 (0%)
Urticaria	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Vascular disorders
Flushing	3/55 (5.5%)		2/54 (3.7%)		1/102 (1%)		3/61 (4.9%)		4/64 (6.3%)		1/122 (0.8%)
Haematoma	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		1/122 (0.8%)
Hot flush	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Hypertension	0/55 (0%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		2/122 (1.6%)
Hypotension	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Peripheral ischaemia	0/55 (0%)		0/54 (0%)		0/102 (0%)		1/61 (1.6%)		0/64 (0%)		0/122 (0%)
Phlebitis superficial	1/55 (1.8%)		0/54 (0%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)
Raynaud's phenomenon	0/55 (0%)		1/54 (1.9%)		0/102 (0%)		0/61 (0%)		0/64 (0%)		0/122 (0%)

Limitations/Caveats

Plasma concentration of PF-00489791 metabolites was not intended as secondary endpoint in the protocol and was considered as an exploratory endpoint.

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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.