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A Research Study To Assess The Effectiveness And Safety Of Different Doses Of Oral PF-00489791 In The Treatment Of Adult Patients With Pulmonary Arterial Hypertension

Sponsor
Pfizer (Industry)
Overall Status
Terminated
CT.gov ID
NCT00853112
Collaborator
(none)
48
Enrollment
25
Locations
7
Arms
15
Actual Duration (Months)
1.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Study will assess PF-00489791 efficacy and safety in Pulmonary Arterial Hypertension (PAH)

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Pfizer decided to stop this trial early upon Stage 1 completion due to change in PF-00489791 development and not as a result of safety concerns for PF-00489791. Date of termination (LSLV) occurred on July 28, 2010.

Study Design

Study Type:
Interventional
Actual Enrollment :
48 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 2a, Randomized, Double Blind, Placebo-controlled, Parallel Group Study Investigating The Dose-response Of Pf-00489791 On Acute Hemodynamics In Subjects With Idiopathic And Familial Pulmonary Arterial Hypertension
Actual Study Start Date :
Apr 1, 2009
Actual Primary Completion Date :
Jul 1, 2010
Actual Study Completion Date :
Jul 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: PF-00489791 1 mg

Drug: PF-00489791
tablet form, 1 mg, single dose (Day 1)
Experimental: PF-00489791 2 mg

Drug: PF-00489791
tablet form, 2 mg, single dose (Day 1)
Experimental: PF-00489791 4 mg

Drug: PF-00489791
tablet form, 4 mg, single dose (Day 1)
Experimental: PF-00489791 10 mg

Drug: PF-00489791
tablet form, 10 mg, single dose (Day 1)
Experimental: PF-00489791 20 mg

Drug: PF-00489791
tablet form, 20 mg, single dose (Day 1)
Placebo Comparator: Placebo

Drug: placebo
tablet form, single dose (Day 1)
Active Comparator: Sildenafil

Observational comparator arm

Drug: sildenafil
tablet form, 20 mg, single dose (Day 1)
Other Names:
  • Revatio

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Mean Change From Baseline in Pulmonary Vascular Resistance Index (PVRI) Over 4 Hours Post Dose [Baseline, up to 4 hours post-dose on Day 1]

      PVRI was calculated as: PVRI (in Wood units*meter^2 [m^2]) = pulmonary vascular resistance (PVR) multiplied by body surface area (BSA). PVR (in Wood units) = (mean pulmonary artery pressure [mean PAP] minus pulmonary capillary wedge pressure [PCWP]) divided by cardiac output (CO, taken as the average of the triplicate measurements). BSA (m^2) = (0.007184) multiplied by (height in centimeters [cm])^0.725 multiplied by (weight in kilograms [kg])^0.425. PVRI values were converted to dyne*second (s)*m^2/centimeter (cm)^5 from Woods units by multiplying by a factor of 79.9. The change from baseline in PVRI over 4-hour interval was calculated as the average of the change from baseline values at 1, 2, 3, and 4 hours post dose on Day 1.

    Secondary Outcome Measures

    1. Greatest Reduction From Baseline in Pulmonary Vascular Resistance Index (PVRI) and Systemic Vascular Resistance Index (SVRI) Over 4 Hours Post Dose [Baseline, up to 4 hours post-dose on Day 1]

      PVRI was calculated as: PVRI (in Wood units*m^2) = PVR multiplied by BSA. PVR (in Wood units) = (mean PAP minus PCWP) divided by CO (taken as the average of the triplicate measurements). SVRI was calculated as: SVRI (Wood units*m^2) = systemic vascular resistance (SVR) multiplied by BSA. SVR (Wood units) = (mean systemic arterial pressure [mean SAP] minus right atrial pressure [RAP]) divided by CO (taken as the average of the triplicate measurements). BSA (m^2) = (0.007184) multiplied by (height in cm)^0.725 multiplied by (weight in kg)^0.425. PVRI and SVRI values were converted to dyne*s*m^2/cm^5 from Woods units by multiplying by a factor of 79.9. For each participant the greatest reduction (GR) from baseline in PVRI and SVRI over 4-hour interval was defined as the maximum reduction (greatest decrease or smallest increase) observed at 1, 2, 3, and 4 hours post dose on Day 1.

    2. Mean Change From Baseline in Systemic Vascular Resistance Index (SVRI) Over 4 Hours Post Dose [Baseline, up to 4 hours post-dose on Day 1]

      SVRI was calculated as: SVRI (Wood units*m^2) = SVR multiplied by BSA. SVR (Wood units) = (mean SAP minus RAP) divided by CO (taken as the average of the triplicate measurements). BSA (m^2) = (0.007184) multiplied by (height in cm)^0.725 multiplied by (weight in kg)^0.425. SVRI values were converted to dyne*s*m^2/cm^5 from Woods units by multiplying by a factor of 79.9. The change from baseline in SVRI over 4-hour interval was calculated as the average of the change from baseline values at 1, 2, 3, and 4 hours post dose on Day 1.

    3. Change From Baseline in Pulmonary Vascular Resistance Index (PVRI) at Hour 1, 2, 3 and 4 Post Dose [Baseline, 1, 2, 3, 4 hours post-dose on Day 1]

      PVRI was calculated as: PVR multiplied by BSA. PVR = (mean PAP minus PCWP) divided by CO (taken as the average of the triplicate measurements). BSA (m^2) = 0.007184 times height (cm)^0.725 times weight (kilogram)^0.425. Wood unit equals to 79.9 dyne*second/cm^5. Hourly changes from baseline in PVRI was reported.

    4. Change From Baseline in Systemic Vascular Resistance Index (SVRI) at Hour 1, 2, 3 and 4 Post Dose [Baseline, 1, 2, 3, 4 hours post-dose on Day 1]

      SVRI is the product of SVR and BSA. SVR equals to (mean SAP subtracted by RAP) divided by CO (taken as the average of the triplicate measurements). BSA (m^2) equals to 0.007184 times height (cm)^0.725 times weight (kilogram) ^0.425. Wood unit equals to 79.9 dyne*second/cm^5. Hourly changes from baseline in SVRI was reported.

    5. Change From Baseline in Cardiac Index (CI) at Hour 1, 2, 3 and 4 Post Dose [Baseline, 1, 2, 3, 4 hours post-dose on Day 1]

      CI was calculated as: CI (liters per minute per square meter [L/min/m^2]) = CO (taken as the average of the triplicate measurements) divided by BSA. BSA (m^2) = (0.007184) multiplied by (height in cm)^0.725 multiplied by (weight in kg)^0.425.

    6. Change From Baseline in Mean Pulmonary Artery Pressure (mPAP), Systolic Pulmonary Artery Pressure (sPAP), Diastolic Pulmonary Artery Pressure (dPAP), Right Atrial Pressure (RAP) at Hour 1, 2, 3 and 4 Post Dose [Baseline, 1, 2, 3, 4 hours post-dose on Day 1]

      Hourly changes from baseline in hemodynamic parameters were reported. Hemodynamic parameters including mPAP, sPAP, dPAP and RAP were measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position. All hemodynamic pressure measurements were performed as triplicate measurements and average was used.

    7. Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP), Mean Systemic Arterial Pressure (SAP), Systolic Systemic Arterial Pressure (sSAP) and Diastolic Systemic Arterial Pressure (dSAP) at Hour 1, 2, 3 and 4 Post Dose [Baseline, 1, 2, 3, 4 hours post-dose on Day 1]

      Hourly changes from baseline in hemodynamic parameters were reported. Hemodynamic parameters including PCWP, SAP, sSAP and dSAP were measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position. All hemodynamic pressure measurements (except PCWP for which 1 measurement is sufficient) were performed as triplicate measurements and average was used.

    8. Mean Change From Baseline in Pulmonary Vascular Resistance (PVR) and Systemic Vascular Resistance (SVR) at Hour 1, 2, 3 and 4 Post Dose [Baseline, 1, 2, 3, 4 hours post-dose on Day 1]

      Hourly changes from baseline in PVR and SVR were reported. PVR was calculated by: PVR (Wood units) = (mean PAP minus PCWP) divided by CO (taken as the average of the triplicate measurements). SVR (Wood units) = (mean SAP minus RAP) divided by CO (taken as the average of the triplicate measurements).

    9. Mean Change From Baseline in Heart Rate (HR) at Hour 1, 2, 3 and 4 Post Dose [Baseline, 1, 2, 3, 4 hours post-dose on Day 1]

      Hourly changes from baseline in HR were reported.

    10. Number of Participants With Clinically Significant Laboratory Values [Baseline up-to follow up (Day 3 to 5)]

      Criteria for clinically significant laboratory values:hemoglobin, hematocrit and red blood cells(less than[<]0.8*lower limit of normal[LLN]); leucocytes (<0.6*LLN/greater than[>]1.5*upper limit of normal[ULN]);platelets (<0.5*LLN></0>1.75* ULN);neutrophils, lymphocytes(<0.8*LLN></0>1.2* ULN); eosinophils, basophils, monocytes (>1.2*ULN);bilirubin (>1.5*ULN);aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase(>3*ULN);creatinine, blood urea nitrogen (>1.3*ULN);glucose(<0.6*LLN></0>1.5* ULN); uric acid(>1.2*ULN);sodium(<0.95*LLN></0>1.05*ULN); potassium, chloride, calcium(<0.9*LLN></0>1.1* ULN); albumin, total protein(<0.8></0>1.2* ULN); creatine kinase(>2.0*ULN);urine red blood cells(RBCs), urine white blood cells(WBCs)(>=6 per high-powered field);qualitative urine glucose, urine ketones, urine protein, urine blood/hemoglobin(>=1); urine bacteria(>20 per high-powered field); pregnancy test, urine protein, quantitative random serum pregnancy test (>=1).

    11. Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Values [Baseline up-to follow up (Day 3 to 5)]

      Criteria for clinically significant changes (changes of potential clinical concern) in ECG parameters: increase from baseline of >=30 to <60 milliseconds (msec) or >=60 msec in corrected QT interval (QTc), QT interval corrected using Fridericia's correction (QTcF) and QT interval corrected using Bazett's correction (QTcB); Increase from baseline of >= 25% (when baseline was >200 msec) or increase from baseline of >=50% (when baseline was <=200 msec) in PR interval; and Increase from baseline of >= 25% (when baseline was >100 msec) or increase from baseline of >=50% (when baseline was <=100 msec) in QRS interval. Number of participants with any clinically significant change in ECG values were reported.

    12. Change From Baseline in Mean Partial Pressure of Oxygen (PaO2) and Carbon Dioxide (PaCO2) at Hour 1 and 4 Post Dose [Baseline; 1, 4 hours post-dose on Day 1]

      Arterial blood samples for PaO2 and PaCO2 collected via an arterial line were assessed. PaO2 is the measure of oxygen level in the arterial blood and PaCO2 is the measure of carbon dioxide level in the arterial blood.

    13. Plasma Concentration of PF-00489791 and Sildenafil [1, 2, 3, 4, 5, 6, 8 hours post-dose on Day 1, follow up (Day 3 to 5)]

    Eligibility Criteria

    Criteria

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

    • Idiopathic or familial pulmonary arterial hypertension (PAH)

    • Mean PAP at least 25 mm Hg, PCWP < 15 mm Hg at rest

    • For females of child-bearing potential negative pregnancy test at screening and use of contraception during the study and 4 weeks after its completion

    • Signed and dated informed consent

    • Willingness to comply with the study plan and procedures

    Exclusion Criteria:

    • pulmonary arterial hypertension (PAH)other than idiopathic or familial

    • For females, pregnancy or lactation

    • Use of specific PAH treatments, potent CYP3A4 inhibitors, protease inhibitors, alpha blockers or arginine 30 days prior tio randomization and during the study

    • Change of dose or class of standard background PAH therapy, i.e. oxygen, calcium channel blockers, digoxin, diuretics 30 days prior tio randomization and during the study

    • Large shift in altitude (defined as >5000 feet or 1524 meters) during 90 days prior to baseline visit and/or during the study visit

    • Subjects with intracardiac shunts and/or serious heart, lung or other health conditions

    • HIV positive subjects

    • Subjects participating in another clinical trial with an investigational drug or device

    • Subjects with degenerative retinal disorders, history of non-arteritic anterior ischemic optic neuropathy or untreated proliferative diabetic retinopathy

    • Allergies and previous intolerance of PDE5 inhibitors

    • Alcohol or drug abuse

    • Blood donation during the study, or 1 month before or after the study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Pulmonary Associates, PA Phoenix Arizona United States 85006
    2 John C. Lincoln Hospital, North Mountain Phoenix Arizona United States 85020
    3 Pulmonary Associates, PA Phoenix Arizona United States 85020
    4 Shands at University of Florida Gainesville Florida United States 32610
    5 Creighton University Medical Center Omaha Nebraska United States 68131
    6 Allegheny General Hospital Pittsburgh Pennsylvania United States 15212
    7 UT Southwestern Medical Center - Department of Internal Medicine Pulmonary Dallas Texas United States 75390
    8 UT Southwestern St. Paul Hospital Dallas Texas United States 75390
    9 Lawson Health Research Institute London Ontario Canada N6A 4G5
    10 London Health Sciences Centre London Ontario Canada N6A 5W9
    11 Sir Mortimer B. Davis, Jewish General Hospital Montreal Quebec Canada H3T 1E2
    12 Thoraxklinik am Universitaetsklinikum Heidelberg Germany 69126
    13 Department Of Cardiology, MediCiti Hospital, Hyderabad Andhra Pardesh India 500 063
    14 Department Of Cardiology, Sri Venkateswara Institute Of Medical Sciences Tirupati Andhra Pardesh India 517 507
    15 Bankers Heart Institute Vadodara Gujarat India 390 015
    16 Omega Hospital Mangalore Karnataka India 575 002
    17 Moscow Healthcare Institution "City Clinical Hospital No. 57" Moscow Russian Federation 105077
    18 Institute of Cardiosurgery n.a. V.I.Burakovsky Moscow Russian Federation 121552
    19 Hospital General Universitari Vall D´Hebron Barcelona Spain 08035
    20 Hospital Clinic I Provincial Barcelona Spain 08036
    21 Hospital Universitario 12 de Octubre Madrid Spain 28041
    22 Universitetssjukhuset i Lund, Hjart- och Lungdivisionen Lund Sweden 221 85
    23 Norrlands Universitetssjukhus, Kliniskt Forsknings Centrum Umea Sweden 901 85
    24 Akademiska Sjukhuset, Kardiologen 50F/Forskningsenheten Uppsala Sweden 751 85
    25 Universitaetsspittal Zuerich, Medizinische Klinik A Zuerich Switzerland CH-8091

    Sponsors and Collaborators

    • Pfizer

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT00853112
    Other Study ID Numbers:
    • A7331009
    • 2008-003572-21
    First Posted:
    Mar 2, 2009
    Last Update Posted:
    Oct 24, 2017
    Last Verified:
    Sep 1, 2017
    Keywords provided by Pfizer
    PAH pulmonary hypertension pulmonary arterial hypertension
    Additional relevant MeSH terms:
    Pulmonary Arterial Hypertension
    Hypertension, Pulmonary
    Hypertension
    Sildenafil Citrate

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1.
    Period Title: Overall Study
    STARTED 6 7 7 8 6 7 7
    Treated 6 6 7 6 6 7 6
    COMPLETED 6 6 7 6 6 7 6
    NOT COMPLETED 0 1 0 2 0 0 1

    Baseline Characteristics

    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil Total
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1. Total of all reporting groups
    Overall Participants 6 6 7 6 6 7 6 44
    Age, Customized (participants) [Number]
    Between 18 and 44 Years
    3
    50%
    2
    33.3%
    4
    57.1%
    5
    83.3%
    2
    33.3%
    2
    28.6%
    3
    50%
    21
    47.7%
    Between 45 and 64 Years
    2
    33.3%
    1
    16.7%
    3
    42.9%
    0
    0%
    2
    33.3%
    3
    42.9%
    2
    33.3%
    13
    29.5%
    Greater than or equal to (>=) 65 Years
    1
    16.7%
    3
    50%
    0
    0%
    1
    16.7%
    2
    33.3%
    2
    28.6%
    1
    16.7%
    10
    22.7%
    Sex: Female, Male (Count of Participants)
    Female
    5
    83.3%
    5
    83.3%
    4
    57.1%
    4
    66.7%
    3
    50%
    5
    71.4%
    4
    66.7%
    30
    68.2%
    Male
    1
    16.7%
    1
    16.7%
    3
    42.9%
    2
    33.3%
    3
    50%
    2
    28.6%
    2
    33.3%
    14
    31.8%

    Outcome Measures

    1. Primary Outcome
    Title Mean Change From Baseline in Pulmonary Vascular Resistance Index (PVRI) Over 4 Hours Post Dose
    Description PVRI was calculated as: PVRI (in Wood units*meter^2 [m^2]) = pulmonary vascular resistance (PVR) multiplied by body surface area (BSA). PVR (in Wood units) = (mean pulmonary artery pressure [mean PAP] minus pulmonary capillary wedge pressure [PCWP]) divided by cardiac output (CO, taken as the average of the triplicate measurements). BSA (m^2) = (0.007184) multiplied by (height in centimeters [cm])^0.725 multiplied by (weight in kilograms [kg])^0.425. PVRI values were converted to dyne*second (s)*m^2/centimeter (cm)^5 from Woods units by multiplying by a factor of 79.9. The change from baseline in PVRI over 4-hour interval was calculated as the average of the change from baseline values at 1, 2, 3, and 4 hours post dose on Day 1.
    Time Frame Baseline, up to 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS) included all randomized participants who received study medication. Here, N (overall number of participants analyzed) = participants evaluable for this measure and 'Number Analyzed' = participants who were evaluable at given time points for each group.
    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1.
    Measure Participants 6 6 7 6 6 6 6
    Baseline
    2026.5
    (1141.94)
    1043.1
    (327.07)
    1602.4
    (990.36)
    1934.3
    (675.31)
    1328.2
    (784.24)
    1380.8
    (1058.35)
    1674.0
    (925.53)
    Change over 4 hours post-dose
    -47.3
    (507.90)
    -106.8
    (136.41)
    11.6
    (213.55)
    -335.3
    (499.52)
    -267.0
    (397.56)
    -254.0
    (361.07)
    304.9
    (799.78)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments Change over 4 hours post-dose: The Bayesian 4-parameter Emax model was used for analysis. 95% credible intervals of the effect size and the posterior distribution were calculated. Posterior distribution was used to calculate a probability (presented as p value) that the dose gives a difference of >=240 dyne*s*m^2/cm^5 from placebo. The predicted means and SD were the posterior means and standard deviation (SD) from the Bayesian analysis.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.120
    Comments
    Method Bayesian 4-parameter Emax model
    Comments
    Method of Estimation Estimation Parameter Predicted Mean Difference
    Estimated Value -115.0
    Confidence Interval (2-Sided) 95%
    -371.5 to -1.1
    Parameter Dispersion Type: Standard Deviation
    Value: 98.36
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments Change over 4 hours post-dose: The Bayesian 4-parameter Emax model was used for analysis. 95% credible intervals of the effect size and the posterior distribution were calculated. Posterior distribution was used to calculate a probability (presented as p value) that the dose gives a difference of >=240 dyne.s.m2/cm5 from placebo. The predicted means and SD were the posterior means and SD from the Bayesian analysis.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.250
    Comments
    Method Bayesian 4-parameter Emax model.
    Comments
    Method of Estimation Estimation Parameter Predicted Mean Difference
    Estimated Value -170.6
    Confidence Interval (2-Sided) 95%
    -409.2 to -7.1
    Parameter Dispersion Type: Standard Deviation
    Value: 107.84
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments The Bayesian 4-parameter Emax model was used for analysis. 95% credible intervals of the effect size and the posterior distribution were calculated. Posterior distribution was used to calculate a probability (presented as p value) that the dose gives a difference of >=240 dyne*s*m^2/cm^5 from placebo. The predicted means and SD were the posterior means and SD from the Bayesian analysis.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.485
    Comments
    Method Bayesian 4-parameter Emax model.
    Comments
    Method of Estimation Estimation Parameter Predicted Mean Difference
    Estimated Value -240.2
    Confidence Interval (2-Sided) 95%
    -444.8 to -33.8
    Parameter Dispersion Type: Standard Deviation
    Value: 109.28
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments Change over 4 hours post-dose: The Bayesian 4-parameter Emax model was used for analysis. 95% credible intervals of the effect size and the posterior distribution were calculated. Posterior distribution was used to calculate a probability (presented as p value) that the dose gives a difference of >=240 dyne*s*m^2/cm^5 from placebo. The predicted means and SD were the posterior means and SD from the Bayesian analysis.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.810
    Comments
    Method Bayesian 4-parameter Emax model.
    Comments
    Method of Estimation Estimation Parameter Predicted Mean Difference
    Estimated Value -327.9
    Confidence Interval (2-Sided) 95%
    -492.9 to -148.0
    Parameter Dispersion Type: Standard Deviation
    Value: 92.41
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments Change over 4 hours post-dose: The Bayesian 4-parameter Emax model was used for analysis. Posterior distribution was calculated and was used to calculate a probability (presented as p value) that the dose gives a difference of >=240 dyne*s*m^2/cm^5 from placebo. The predicted means and SD were the posterior means and SD from the Bayesian analysis.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.974
    Comments
    Method Bayesian 4-parameter Emax model
    Comments
    Method of Estimation Estimation Parameter Predicted Mean Difference
    Estimated Value -379.4
    Confidence Interval (2-Sided) 95%
    -520.6 to -238.8
    Parameter Dispersion Type: Standard Deviation
    Value: 73.61
    Estimation Comments
    2. Secondary Outcome
    Title Greatest Reduction From Baseline in Pulmonary Vascular Resistance Index (PVRI) and Systemic Vascular Resistance Index (SVRI) Over 4 Hours Post Dose
    Description PVRI was calculated as: PVRI (in Wood units*m^2) = PVR multiplied by BSA. PVR (in Wood units) = (mean PAP minus PCWP) divided by CO (taken as the average of the triplicate measurements). SVRI was calculated as: SVRI (Wood units*m^2) = systemic vascular resistance (SVR) multiplied by BSA. SVR (Wood units) = (mean systemic arterial pressure [mean SAP] minus right atrial pressure [RAP]) divided by CO (taken as the average of the triplicate measurements). BSA (m^2) = (0.007184) multiplied by (height in cm)^0.725 multiplied by (weight in kg)^0.425. PVRI and SVRI values were converted to dyne*s*m^2/cm^5 from Woods units by multiplying by a factor of 79.9. For each participant the greatest reduction (GR) from baseline in PVRI and SVRI over 4-hour interval was defined as the maximum reduction (greatest decrease or smallest increase) observed at 1, 2, 3, and 4 hours post dose on Day 1.
    Time Frame Baseline, up to 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    Full analysis set (FAS) included all randomized participants who received study medication. Here, N (overall number of participants analyzed) = participants evaluable for this measure and 'Number Analyzed' = participants who were evaluable at given time points for each group.
    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1.
    Measure Participants 6 6 7 6 6 6 6
    Baseline: SVRI
    3560.6
    (1481.67)
    2512.2
    (858.62)
    2599.6
    (874.85)
    3679.1
    (1248.03)
    3175.8
    (644.80)
    2577.1
    (791.93)
    3121.8
    (544.52)
    GR over 4 hours: PVRI
    -180.8
    (487.37)
    -210.2
    (132.60)
    -143.4
    (188.58)
    -600.9
    (453.38)
    -397.8
    (386.51)
    -385.9
    (455.07)
    55.8
    (526.85)
    GR over 4 hours: SVRI
    -806.1
    (480.86)
    -387.6
    (428.39)
    -394.1
    (594.61)
    -1110.5
    (1079.75)
    -1000.6
    (529.43)
    -524.1
    (370.71)
    -113.6
    (726.61)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments GR over 4 hours, PVRI: The analysis was performed using Analysis of Covariance (ANCOVA) with baseline fitted as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.354
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -195.3
    Confidence Interval (2-Sided) 95%
    -618.8 to 228.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 207.38
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments GR over 4 hours, PVRI: The analysis was performed using ANCOVA with baseline fitted as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.860
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -34.1
    Confidence Interval (2-Sided) 95%
    -424.1 to 356.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 190.99
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments GR over 4 hours, PVRI: The analysis was performed using ANCOVA with baseline fitted as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.034
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -435.7
    Confidence Interval (2-Sided) 95%
    -835.9 to -35.6
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 195.94
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments GR over 4 hours, PVRI: The analysis was performed using ANCOVA with baseline fitted as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.107
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -334.7
    Confidence Interval (2-Sided) 95%
    -746.7 to 77.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 201.74
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments GR over 4 hours, PVRI: The analysis was performed using ANCOVA with baseline fitted as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.177
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -278.0
    Confidence Interval (2-Sided) 95%
    -688.3 to 132.2
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 200.89
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments GR over 4 hours, SVRI: The analysis was performed using ANCOVA with baseline fitted as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.873
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 51.1
    Confidence Interval (2-Sided) 95%
    -594.1 to 696.3
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 315.91
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments GR over 4 hours, SVRI: The analysis was performed using ANCOVA with baseline fitted as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.806
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 75.2
    Confidence Interval (2-Sided) 95%
    -543.8 to 694.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 303.08
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments GR over 4 hours, SVRI: The analysis was performed using ANCOVA with baseline fitted as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.390
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -262.8
    Confidence Interval (2-Sided) 95%
    -877.8 to 352.1
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 301.10
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments GR over 4 hours, SVRI: The analysis was performed using ANCOVA with baseline fitted as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.286
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -329.4
    Confidence Interval (2-Sided) 95%
    -948.1 to 289.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 302.97
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments GR over 4 hours, SVRI: The analysis was performed using ANCOVA with baseline fitted as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.843
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -62.7
    Confidence Interval (2-Sided) 95%
    -704.3 to 578.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 314.15
    Estimation Comments
    3. Secondary Outcome
    Title Mean Change From Baseline in Systemic Vascular Resistance Index (SVRI) Over 4 Hours Post Dose
    Description SVRI was calculated as: SVRI (Wood units*m^2) = SVR multiplied by BSA. SVR (Wood units) = (mean SAP minus RAP) divided by CO (taken as the average of the triplicate measurements). BSA (m^2) = (0.007184) multiplied by (height in cm)^0.725 multiplied by (weight in kg)^0.425. SVRI values were converted to dyne*s*m^2/cm^5 from Woods units by multiplying by a factor of 79.9. The change from baseline in SVRI over 4-hour interval was calculated as the average of the change from baseline values at 1, 2, 3, and 4 hours post dose on Day 1.
    Time Frame Baseline, up to 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomized participants who received study medication. Here, N (overall number of participants analyzed) = participants evaluable for this measure.
    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1.
    Measure Participants 6 6 7 6 6 6 6
    Mean (Standard Deviation) [(dyne*s*m^2)/cm^5]
    -486.8
    (543.83)
    -193.9
    (336.10)
    -145.7
    (557.67)
    -609.6
    (1061.78)
    -704.7
    (501.01)
    -272.8
    (228.53)
    97.6
    (810.82)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments The analysis was performed using ANCOVA with baseline fitted as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.999
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -0.4
    Confidence Interval (2-Sided) 95%
    -659.7 to 658.8
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 322.80
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments The analysis was performed using ANCOVA with baseline fitted as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.817
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 72.2
    Confidence Interval (2-Sided) 95%
    -560.2 to 704.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 309.69
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments The analysis was performed using ANCOVA with baseline fitted as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.790
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -82.6
    Confidence Interval (2-Sided) 95%
    -711.0 to 545.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 307.67
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments The analysis was performed using ANCOVA with baseline fitted as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.301
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -325.6
    Confidence Interval (2-Sided) 95%
    -957.8 to 306.7
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 309.58
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments The analysis was performed using ANCOVA with baseline fitted as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.850
    Comments
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -61.2
    Confidence Interval (2-Sided) 95%
    -716.8 to 594.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 321.00
    Estimation Comments
    4. Secondary Outcome
    Title Change From Baseline in Pulmonary Vascular Resistance Index (PVRI) at Hour 1, 2, 3 and 4 Post Dose
    Description PVRI was calculated as: PVR multiplied by BSA. PVR = (mean PAP minus PCWP) divided by CO (taken as the average of the triplicate measurements). BSA (m^2) = 0.007184 times height (cm)^0.725 times weight (kilogram)^0.425. Wood unit equals to 79.9 dyne*second/cm^5. Hourly changes from baseline in PVRI was reported.
    Time Frame Baseline, 1, 2, 3, 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomized participants who received study medication. Here, N (overall number of participants analyzed) = participants evaluable for this measure and 'Number Analyzed' = participants who were evaluable at given time points for each group.
    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1.
    Measure Participants 6 6 7 6 6 6 6
    Change at hour 1
    32.03
    (637.84)
    -121.86
    (228.17)
    -15.84
    (245.75)
    -333.75
    (482.43)
    -228.30
    (526.40)
    -183.51
    (123.88)
    121.33
    (449.03)
    Change at hour 2
    -84.78
    (554.32)
    -167.42
    (169.75)
    2.91
    (216.15)
    -210.86
    (779.62)
    -302.42
    (378.43)
    -315.71
    (441.19)
    252.41
    (891.95)
    Change at hour 3
    -51.15
    (501.81)
    -22.45
    (182.54)
    16.64
    (272.36)
    -326.88
    (815.60)
    -244.54
    (367.99)
    -276.37
    (519.49)
    392.24
    (859.17)
    Change at hour 4
    -85.20
    (406.10)
    -115.49
    (172.46)
    42.55
    (321.24)
    -416.28
    (420.63)
    -292.65
    (399.71)
    -240.48
    (422.15)
    453.54
    (1012.97)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments Change at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.295
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -269.32
    Confidence Interval (2-Sided) 95%
    -785.39 to 246.76
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 252.93
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments Change at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.680
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -97.65
    Confidence Interval (2-Sided) 95%
    -577.02 to 381.72
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 234.55
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments Change at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.129
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -376.61
    Confidence Interval (2-Sided) 95%
    -869.53 to 116.31
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 241.06
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments Change at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.176
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -342.29
    Confidence Interval (2-Sided) 95%
    -846.90 to 162.32
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 247.07
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments Hour 1: Longitudinal analysis was used to analyze p-value and included baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.235
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -316.86
    Confidence Interval (2-Sided) 95%
    -850.90 to 217.17
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 261.58
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments Change at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.430
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -198.06
    Confidence Interval (2-Sided) 95%
    -705.04 to 308.91
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 247.62
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments Change at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.870
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 37.90
    Confidence Interval (2-Sided) 95%
    -432.23 to 508.04
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 229.23
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments Change at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.645
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -114.06
    Confidence Interval (2-Sided) 95%
    -614.57 to 386.45
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 244.95
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments Change at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.225
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -299.60
    Confidence Interval (2-Sided) 95%
    -794.81 to 195.61
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 241.63
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments Change at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.205
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -332.25
    Confidence Interval (2-Sided) 95%
    -856.55 to 192.05
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 255.93
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments Change at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.745
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -86.72
    Confidence Interval (2-Sided) 95%
    -625.87 to 452.42
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 263.63
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments Change at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.942
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 18.00
    Confidence Interval (2-Sided) 95%
    -484.46 to 520.47
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 245.25
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments Change at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.314
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -265.94
    Confidence Interval (2-Sided) 95%
    -796.15 to 264.28
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 259.53
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments Change at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.295
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -275.35
    Confidence Interval (2-Sided) 95%
    -803.57 to 252.88
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 258.01
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments Change at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.241
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -326.55
    Confidence Interval (2-Sided) 95%
    -885.12 to 232.02
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 272.96
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments Change at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.510
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -145.71
    Confidence Interval (2-Sided) 95%
    -592.24 to 300.83
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 218.50
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments Change at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.699
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 77.96
    Confidence Interval (2-Sided) 95%
    -330.70 to 486.63
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 199.85
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments Change at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.106
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -341.91
    Confidence Interval (2-Sided) 95%
    -760.45 to 76.64
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 204.65
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments Change at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.182
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -289.41
    Confidence Interval (2-Sided) 95%
    -722.17 to 143.35
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 211.69
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments Change at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.263
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -256.60
    Confidence Interval (2-Sided) 95%
    -716.26 to 203.06
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 224.88
    Estimation Comments
    5. Secondary Outcome
    Title Change From Baseline in Systemic Vascular Resistance Index (SVRI) at Hour 1, 2, 3 and 4 Post Dose
    Description SVRI is the product of SVR and BSA. SVR equals to (mean SAP subtracted by RAP) divided by CO (taken as the average of the triplicate measurements). BSA (m^2) equals to 0.007184 times height (cm)^0.725 times weight (kilogram) ^0.425. Wood unit equals to 79.9 dyne*second/cm^5. Hourly changes from baseline in SVRI was reported.
    Time Frame Baseline, 1, 2, 3, 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomized participants who received study medication. Here, N (overall number of participants analyzed) = participants evaluable for this measure and 'Number Analyzed' = participants who were evaluable at given time points for each group.
    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1.
    Measure Participants 6 6 7 6 6 6 6
    Change at hour 1
    -278.74
    (812.16)
    -281.26
    (386.52)
    -145.25
    (712.56)
    -602.63
    (993.10)
    -616.40
    (674.29)
    -48.54
    (218.85)
    125.71
    (607.77)
    Change at hour 2
    -518.41
    (533.85)
    -308.47
    (487.47)
    -222.83
    (550.92)
    -381.01
    (1069.58)
    -893.81
    (479.01)
    -347.45
    (392.26)
    34.44
    (959.10)
    Change at hour 3
    -489.10
    (531.15)
    -115.91
    (321.47)
    -92.23
    (551.76)
    -502.93
    (1390.25)
    -739.16
    (485.07)
    -369.29
    (423.35)
    79.04
    (844.22)
    Change at hour 4
    -660.98
    (524.55)
    -69.89
    (290.88)
    -122.36
    (560.20)
    -874.51
    (1171.91)
    -569.43
    (581.07)
    -325.95
    (372.51)
    151.18
    (902.51)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments Change at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.401
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -328.10
    Confidence Interval (2-Sided) 95%
    -1114.11 to 457.92
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 385.78
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments Change at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.659
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -164.96
    Confidence Interval (2-Sided) 95%
    -920.05 to 590.12
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 370.54
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments Change at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.447
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -287.08
    Confidence Interval (2-Sided) 95%
    -1047.59 to 473.42
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 372.60
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments Change at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.231
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -457.16
    Confidence Interval (2-Sided) 95%
    -1220.86 to 306.53
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 374.26
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments Change at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.846
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -75.24
    Confidence Interval (2-Sided) 95%
    -858.19 to 707.71
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 384.20
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments Change at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.748
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -115.64
    Confidence Interval (2-Sided) 95%
    -844.24 to 612.96
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 357.20
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments Change at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.993
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -2.87
    Confidence Interval (2-Sided) 95%
    -702.41 to 696.67
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 342.91
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments Change at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.615
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 174.20
    Confidence Interval (2-Sided) 95%
    -526.41 to 874.81
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 342.93
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments Change at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.161
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -494.91
    Confidence Interval (2-Sided) 95%
    -1199.04 to 209.21
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 344.72
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments Change at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.708
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -134.48
    Confidence Interval (2-Sided) 95%
    -859.74 to 590.77
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 355.50
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments Change at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.897
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 47.61
    Confidence Interval (2-Sided) 95%
    -697.56 to 792.79
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 365.43
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments Change at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.781
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 98.42
    Confidence Interval (2-Sided) 95%
    -617.15 to 813.99
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 350.87
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments Change at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.937
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -28.31
    Confidence Interval (2-Sided) 95%
    -753.46 to 696.83
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 355.47
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments Change at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.304
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -369.57
    Confidence Interval (2-Sided) 95%
    -1090.86 to 351.72
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 353.25
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments Change at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.613
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -185.64
    Confidence Interval (2-Sided) 95%
    -927.54 to 556.27
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 363.77
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments Change at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.420
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 265.51
    Confidence Interval (2-Sided) 95%
    -397.45 to 928.48
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 324.88
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments Change at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.447
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 240.17
    Confidence Interval (2-Sided) 95%
    -395.81 to 876.14
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 311.63
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments Change at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.572
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -176.74
    Confidence Interval (2-Sided) 95%
    -808.10 to 454.63
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 309.11
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments Change at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.929
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -27.96
    Confidence Interval (2-Sided) 95%
    -663.31 to 607.38
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 311.11
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments Change at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.928
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 29.58
    Confidence Interval (2-Sided) 95%
    -629.62 to 688.79
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 323.01
    Estimation Comments
    6. Secondary Outcome
    Title Change From Baseline in Cardiac Index (CI) at Hour 1, 2, 3 and 4 Post Dose
    Description CI was calculated as: CI (liters per minute per square meter [L/min/m^2]) = CO (taken as the average of the triplicate measurements) divided by BSA. BSA (m^2) = (0.007184) multiplied by (height in cm)^0.725 multiplied by (weight in kg)^0.425.
    Time Frame Baseline, 1, 2, 3, 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomized participants who received study medication. Here, N (overall number of participants analyzed) = participants evaluable for this measure and 'Number Analyzed' = participants who were evaluable at given time points for each group.
    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1.
    Measure Participants 6 6 7 6 6 6 6
    Baseline
    1.90
    (0.50)
    2.90
    (0.69)
    2.99
    (1.61)
    2.05
    (0.55)
    2.30
    (0.40)
    3.07
    (1.47)
    2.43
    (0.70)
    Change at hour 1
    0.12
    (0.25)
    0.20
    (0.57)
    -0.06
    (0.67)
    0.27
    (0.36)
    0.49
    (0.67)
    -0.13
    (0.21)
    -0.15
    (0.31)
    Change at hour 2
    0.22
    (0.24)
    0.36
    (0.78)
    0.09
    (0.65)
    0.17
    (0.46)
    0.59
    (0.41)
    0.14
    (0.88)
    -0.11
    (0.45)
    Change at hour 3
    0.19
    (0.29)
    0.12
    (0.31)
    -0.15
    (0.77)
    0.19
    (0.41)
    0.54
    (0.62)
    0.19
    (0.63)
    -0.24
    (0.26)
    Change at hour 4
    0.20
    (0.36)
    0.10
    (0.56)
    -0.12
    (0.59)
    0.36
    (0.30)
    0.38
    (0.54)
    0.26
    (0.38)
    -0.27
    (0.29)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments Change at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.412
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 0.24
    Confidence Interval (2-Sided) 95%
    -0.35 to 0.83
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.29
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments Change at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.999
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 0.00
    Confidence Interval (2-Sided) 95%
    -0.58 to 0.58
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.28
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments Change at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.535
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 0.17
    Confidence Interval (2-Sided) 95%
    -0.39 to 0.74
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.28
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments Change at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.128
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 0.44
    Confidence Interval (2-Sided) 95%
    -0.13 to 1.01
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.28
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments Change at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.823
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -0.07
    Confidence Interval (2-Sided) 95%
    -0.67 to 0.53
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.29
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments Change at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.396
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 0.29
    Confidence Interval (2-Sided) 95%
    -0.40 to 0.99
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.34
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments Change at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.899
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 0.04
    Confidence Interval (2-Sided) 95%
    -0.63 to 0.72
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.33
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments Change at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.928
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -0.03
    Confidence Interval (2-Sided) 95%
    -0.70 to 0.64
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.33
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments Change at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.203
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 0.43
    Confidence Interval (2-Sided) 95%
    -0.25 to 1.11
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.33
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments Change at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.772
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 0.10
    Confidence Interval (2-Sided) 95%
    -0.60 to 0.80
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.34
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments Change at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.771
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 0.09
    Confidence Interval (2-Sided) 95%
    -0.52 to 0.69
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.29
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments Change at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.572
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -0.16
    Confidence Interval (2-Sided) 95%
    -0.75 to 0.42
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.29
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments Change at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.966
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 0.01
    Confidence Interval (2-Sided) 95%
    -0.58 to 0.60
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.29
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments Change at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.157
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 0.41
    Confidence Interval (2-Sided) 95%
    -0.17 to 1.00
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.28
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments Change at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.546
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 0.18
    Confidence Interval (2-Sided) 95%
    -0.43 to 0.79
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.30
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments Change at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.818
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 0.07
    Confidence Interval (2-Sided) 95%
    -0.51 to 0.64
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.28
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments Change at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.603
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -0.14
    Confidence Interval (2-Sided) 95%
    -0.71 to 0.42
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.28
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments Change at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.495
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 0.19
    Confidence Interval (2-Sided) 95%
    -0.37 to 0.74
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.27
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments Change at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.375
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 0.24
    Confidence Interval (2-Sided) 95%
    -0.31 to 0.80
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.27
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments Change at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.392
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value 0.25
    Confidence Interval (2-Sided) 95%
    -0.34 to 0.84
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.29
    Estimation Comments
    7. Secondary Outcome
    Title Change From Baseline in Mean Pulmonary Artery Pressure (mPAP), Systolic Pulmonary Artery Pressure (sPAP), Diastolic Pulmonary Artery Pressure (dPAP), Right Atrial Pressure (RAP) at Hour 1, 2, 3 and 4 Post Dose
    Description Hourly changes from baseline in hemodynamic parameters were reported. Hemodynamic parameters including mPAP, sPAP, dPAP and RAP were measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position. All hemodynamic pressure measurements were performed as triplicate measurements and average was used.
    Time Frame Baseline, 1, 2, 3, 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomized participants who received study medication. Here, 'Number Analyzed' = participants who were evaluable at given time points for each group.
    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1.
    Measure Participants 6 6 7 6 6 7 6
    Baseline: mPAP
    53.67
    (15.36)
    45.67
    (13.47)
    60.29
    (22.32)
    53.83
    (11.34)
    44.95
    (18.98)
    50.17
    (23.25)
    55.33
    (18.49)
    Baseline: sPAP
    88.3
    (20.69)
    71.2
    (17.84)
    84.1
    (32.62)
    83.8
    (24.26)
    68.2
    (28.93)
    68.6
    (29.53)
    82.5
    (28.13)
    Baseline: dPAP
    34.5
    (13.28)
    29.3
    (12.86)
    45.0
    (17.51)
    35.7
    (8.71)
    29.7
    (14.68)
    39.1
    (18.41)
    41.0
    (16.63)
    Baseline: RAP
    11.5
    (5.01)
    5.3
    (3.72)
    9.3
    (2.21)
    8.5
    (4.32)
    5.7
    (1.37)
    8.3
    (3.64)
    6.5
    (3.27)
    mPAP: Change at hour 1
    2.17
    (8.89)
    -3.00
    (4.47)
    -2.00
    (5.23)
    -1.50
    (7.69)
    0.38
    (6.23)
    -6.00
    (4.43)
    -2.67
    (6.92)
    sPAP: Change at hour 1
    1.0
    (13.96)
    -5.3
    (5.79)
    -3.3
    (6.52)
    -3.0
    (13.19)
    -2.8
    (10.34)
    -7.0
    (8.21)
    -6.5
    (11.15)
    dPAP: Change at hour 1
    2.2
    (6.68)
    -0.3
    (5.09)
    -2.3
    (4.61)
    -0.5
    (6.72)
    4.7
    (6.59)
    -6.4
    (5.86)
    -2.0
    (3.03)
    RAP: Change at hour 1
    0.3
    (1.03)
    1.2
    (1.47)
    -1.0
    (1.83)
    -1.3
    (2.73)
    0.2
    (1.47)
    -1.4
    (2.99)
    -0.3
    (1.37)
    mPAP: Change at hour 2
    2.83
    (7.17)
    -3.67
    (4.72)
    1.29
    (5.74)
    -0.83
    (6.77)
    1.05
    (5.12)
    -5.50
    (4.14)
    -1.00
    (6.07)
    sPAP: Change at hour 2
    8.3
    (13.47)
    -8.5
    (8.92)
    -0.6
    (8.92)
    -4.2
    (11.46)
    -1.7
    (7.92)
    -6.4
    (7.37)
    -6.5
    (8.19)
    dPAP: Change at hour 2
    0.7
    (3.50)
    -0.5
    (7.34)
    1.6
    (4.65)
    -0.5
    (7.26)
    3.8
    (6.05)
    -7.3
    (3.55)
    -0.3
    (3.61)
    RAP: Change at hour 2
    1.0
    (1.55)
    0.0
    (1.10)
    -1.0
    (1.83)
    -1.5
    (1.87)
    0.5
    (1.76)
    -1.0
    (2.52)
    0.0
    (1.90)
    mPAP: Change at hour 3
    2.83
    (5.27)
    1.17
    (7.94)
    -1.71
    (7.80)
    -3.17
    (3.87)
    2.10
    (6.64)
    -6.33
    (5.96)
    -0.67
    (7.50)
    sPAP: Change at hour 3
    5.0
    (5.83)
    -2.8
    (7.63)
    -5.0
    (10.88)
    -4.0
    (10.83)
    -1.3
    (10.35)
    -8.6
    (10.49)
    -4.5
    (8.92)
    dPAP: Change at hour 3
    1.7
    (6.53)
    3.3
    (10.60)
    -0.4
    (5.50)
    -1.8
    (4.49)
    4.8
    (9.11)
    -6.7
    (5.44)
    -1.3
    (2.94)
    RAP: Change at hour 3
    1.3
    (3.01)
    0.5
    (1.38)
    -1.1
    (2.27)
    0.8
    (5.04)
    0.7
    (2.25)
    -2.4
    (3.51)
    -0.2
    (1.72)
    mPAP: Change at hour 4
    2.67
    (6.47)
    -3.50
    (5.54)
    -0.86
    (9.32)
    -2.50
    (2.74)
    -0.28
    (6.48)
    -6.33
    (6.53)
    -0.67
    (9.03)
    sPAP: Change at hour 4
    0.3
    (11.91)
    -7.7
    (10.56)
    -4.9
    (14.42)
    -3.3
    (10.23)
    -8.7
    (8.76)
    -4.9
    (11.58)
    -3.7
    (11.60)
    dPAP: Change at hour 4
    3.7
    (6.77)
    -0.7
    (5.54)
    1.1
    (7.03)
    -2.2
    (4.36)
    5.3
    (8.26)
    -8.9
    (8.59)
    -1.0
    (4.20)
    RAP: Change at hour 4
    1.2
    (2.71)
    1.0
    (2.00)
    -0.7
    (2.56)
    0.0
    (4.60)
    0.3
    (2.42)
    -1.7
    (3.09)
    0.5
    (3.33)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments mPAP at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.210
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -4.80
    Confidence Interval (2-Sided) 95%
    -12.47 to 2.86
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.75
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments mPAP at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.225
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -4.47
    Confidence Interval (2-Sided) 95%
    -11.84 to 2.90
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.61
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments mPAP at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.332
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -3.67
    Confidence Interval (2-Sided) 95%
    -11.28 to 3.93
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.73
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments mPAP at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.714
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -1.39
    Confidence Interval (2-Sided) 95%
    -9.06 to 6.28
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.76
    Estimation Comments
    Statistical Analysis 5
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments mPAP at Hour 1: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.040
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -8.01
    Confidence Interval (2-Sided) 95%
    -15.63 to -0.39
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.73
    Estimation Comments
    Statistical Analysis 6
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments mPAP at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.079
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -6.14
    Confidence Interval (2-Sided) 95%
    -13.02 to 0.75
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.37
    Estimation Comments
    Statistical Analysis 7
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments mPAP at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.573
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -1.85
    Confidence Interval (2-Sided) 95%
    -8.46 to 4.77
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.24
    Estimation Comments
    Statistical Analysis 8
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments mPAP at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.280
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -3.67
    Confidence Interval (2-Sided) 95%
    -10.50 to 3.15
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.34
    Estimation Comments
    Statistical Analysis 9
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments mPAP at Hour 2: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.684
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -1.39
    Confidence Interval (2-Sided) 95%
    -8.28 to 5.51
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.38
    Estimation Comments
    Statistical Analysis 10
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments mPAP at Hour 2: Longitudinal analysis was used to analyze p-value and included baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.021
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -8.17
    Confidence Interval (2-Sided) 95%
    -15.01 to -1.34
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.35
    Estimation Comments
    Statistical Analysis 11
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments mPAP at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.727
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -1.30
    Confidence Interval (2-Sided) 95%
    -8.86 to 6.25
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.70
    Estimation Comments
    Statistical Analysis 12
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments mPAP at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.183
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -4.85
    Confidence Interval (2-Sided) 95%
    -12.12 to 2.42
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.56
    Estimation Comments
    Statistical Analysis 13
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments mPAP at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.112
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -6.01
    Confidence Interval (2-Sided) 95%
    -13.51 to 1.49
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.67
    Estimation Comments
    Statistical Analysis 14
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments mPAP at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.928
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -0.34
    Confidence Interval (2-Sided) 95%
    -7.91 to 7.23
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.71
    Estimation Comments
    Statistical Analysis 15
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments mPAP at Hour 3: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.020
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -9.01
    Confidence Interval (2-Sided) 95%
    -16.52 to -1.50
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.68
    Estimation Comments
    Statistical Analysis 16
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 1 mg
    Comments mPAP at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.136
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -5.80
    Confidence Interval (2-Sided) 95%
    -13.55 to 1.94
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.79
    Estimation Comments
    Statistical Analysis 17
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 2 mg
    Comments mPAP at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.303
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -3.82
    Confidence Interval (2-Sided) 95%
    -11.27 to 3.63
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.65
    Estimation Comments
    Statistical Analysis 18
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 4 mg
    Comments mPAP at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.180
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -5.17
    Confidence Interval (2-Sided) 95%
    -12.87 to 2.52
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.77
    Estimation Comments
    Statistical Analysis 19
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 10 mg
    Comments mPAP at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.506
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -2.56
    Confidence Interval (2-Sided) 95%
    -10.31 to 5.20
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.80
    Estimation Comments
    Statistical Analysis 20
    Statistical Analysis Overview Comparison Group Selection Placebo, PF-00489791 20 mg
    Comments mPAP at Hour 4: The analysis was performed using longitudinal analysis model with baseline as a covariate.
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.026
    Comments
    Method Longitudinal analysis
    Comments
    Method of Estimation Estimation Parameter Adjusted Mean Difference
    Estimated Value -8.84
    Confidence Interval (2-Sided) 95%
    -16.54 to -1.14
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.77
    Estimation Comments
    8. Secondary Outcome
    Title Change From Baseline in Pulmonary Capillary Wedge Pressure (PCWP), Mean Systemic Arterial Pressure (SAP), Systolic Systemic Arterial Pressure (sSAP) and Diastolic Systemic Arterial Pressure (dSAP) at Hour 1, 2, 3 and 4 Post Dose
    Description Hourly changes from baseline in hemodynamic parameters were reported. Hemodynamic parameters including PCWP, SAP, sSAP and dSAP were measured using a pressure transducer positioned at the mid-axillary line with the participant in the supine position. All hemodynamic pressure measurements (except PCWP for which 1 measurement is sufficient) were performed as triplicate measurements and average was used.
    Time Frame Baseline, 1, 2, 3, 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomized participants who received study medication. Here, 'Number Analyzed' = participants who were evaluable at given time points for each group.
    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1.
    Measure Participants 6 6 7 6 6 7 6
    Baseline: PCWP
    11.0
    (1.79)
    8.2
    (3.76)
    11.7
    (1.70)
    7.3
    (3.56)
    9.5
    (2.07)
    10.4
    (2.88)
    10.2
    (1.72)
    Baseline: SAP
    89.2
    (14.06)
    91.0
    (13.78)
    91.6
    (11.62)
    96.0
    (12.70)
    94.7
    (10.69)
    95.5
    (9.50)
    97.5
    (10.58)
    Baseline: sSAP
    122.5
    (12.76)
    132.0
    (19.45)
    116.9
    (6.07)
    131.2
    (8.80)
    131.5
    (15.67)
    126.5
    (23.37)
    128.3
    (15.81)
    Baseline: dSAP
    71.3
    (12.55)
    67.0
    (9.55)
    74.9
    (12.81)
    77.2
    (12.19)
    71.0
    (8.46)
    78.2
    (7.03)
    79.3
    (7.00)
    PCWP: Change at hour 1
    -0.5
    (2.43)
    0.3
    (3.08)
    -0.3
    (0.49)
    0.8
    (1.72)
    0.3
    (1.37)
    -1.7
    (2.80)
    -0.6
    (1.52)
    SAP: Change at hour 1
    -2.0
    (7.13)
    -5.8
    (9.70)
    -5.9
    (7.93)
    -6.3
    (6.12)
    -1.4
    (6.36)
    -6.7
    (7.47)
    -4.2
    (6.08)
    sSAP: Change at hour 1
    2.3
    (17.11)
    -9.5
    (16.28)
    -0.6
    (11.52)
    -7.2
    (5.64)
    -2.3
    (11.96)
    -7.3
    (8.16)
    -5.2
    (6.08)
    dSAP: Change at hour 1
    -0.7
    (1.63)
    -4.3
    (7.03)
    -6.7
    (8.96)
    -5.0
    (6.03)
    -0.7
    (4.23)
    -7.2
    (5.64)
    -3.5
    (5.82)
    PCWP: Change at hour 2
    0.2
    (2.48)
    -0.3
    (2.34)
    -1.0
    (1.15)
    0.0
    (0.82)
    -0.2
    (1.33)
    -1.7
    (2.16)
    -0.4
    (1.14)
    SAP: Change at hour 2
    -3.3
    (7.03)
    -6.1
    (8.75)
    -3.3
    (10.00)
    -5.3
    (6.02)
    -6.1
    (11.44)
    -6.8
    (6.55)
    -8.8
    (10.07)
    sSAP: Change at hour 2
    -0.5
    (13.90)
    -8.2
    (14.93)
    -0.7
    (15.90)
    -6.0
    (4.90)
    -5.2
    (12.84)
    -5.8
    (9.66)
    -10.3
    (13.17)
    dSAP: Change at hour 2
    -2.5
    (4.46)
    -4.3
    (7.26)
    -3.0
    (9.87)
    -3.0
    (5.10)
    -4.5
    (8.19)
    -7.7
    (5.85)
    -7.5
    (8.09)
    PCWP: Change at hour 3
    -0.3
    (2.07)
    0.8
    (2.56)
    -0.7
    (1.11)
    0.3
    (0.96)
    1.0
    (4.00)
    -0.8
    (1.30)
    -0.6
    (1.52)
    SAP: Change at hour 3
    -2.5
    (9.20)
    -1.5
    (5.86)
    -4.7
    (9.09)
    -7.0
    (8.60)
    -1.7
    (22.10)
    -10.5
    (8.71)
    -10.8
    (12.09)
    sSAP: Change at hour 3
    -0.3
    (14.01)
    -5.5
    (11.15)
    1.3
    (14.34)
    -8.0
    (10.66)
    -9.2
    (16.15)
    -9.3
    (13.75)
    -12.2
    (16.13)
    dSAP: Change at hour 3
    -1.3
    (5.82)
    -1.2
    (5.04)
    -5.4
    (8.70)
    -6.7
    (7.97)
    -1.0
    (15.03)
    -9.5
    (5.17)
    -9.2
    (10.30)
    PCWP: Change at hour 4
    -0.7
    (1.51)
    0.8
    (2.32)
    -0.1
    (1.35)
    -0.7
    (1.51)
    1.7
    (3.78)
    -1.0
    (1.87)
    0.0
    (0.00)
    SAP: Change at hour 4
    -5.8
    (9.02)
    -4.3
    (4.63)
    -4.6
    (7.63)
    -4.3
    (10.35)
    -2.2
    (8.08)
    -9.0
    (9.55)
    -8.8
    (11.86)
    sSAP: Change at hour 4
    -1.3
    (16.24)
    -4.3
    (9.69)
    -1.7
    (12.41)
    -6.8
    (13.63)
    -4.7
    (14.12)
    -9.3
    (15.13)
    -10.8
    (13.69)
    dSAP: Change at hour 4
    -2.8
    (7.36)
    -2.3
    (4.13)
    -4.1
    (8.05)
    -3.7
    (10.46)
    -0.8
    (6.11)
    -7.7
    (5.01)
    -7.5
    (10.88)
    9. Secondary Outcome
    Title Mean Change From Baseline in Pulmonary Vascular Resistance (PVR) and Systemic Vascular Resistance (SVR) at Hour 1, 2, 3 and 4 Post Dose
    Description Hourly changes from baseline in PVR and SVR were reported. PVR was calculated by: PVR (Wood units) = (mean PAP minus PCWP) divided by CO (taken as the average of the triplicate measurements). SVR (Wood units) = (mean SAP minus RAP) divided by CO (taken as the average of the triplicate measurements).
    Time Frame Baseline, 1, 2, 3, 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomized participants who received study medication. Here, 'Number Analyzed' = participants who were evaluable at given time points for each group.
    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1.
    Measure Participants 6 6 7 6 6 7 6
    PVR: Baseline
    1217.0
    (765.98)
    665.1
    (267.93)
    995.3
    (638.42)
    1117.2
    (523.04)
    820.5
    (565.07)
    815.4
    (600.27)
    966.6
    (441.55)
    SVR: Baseline
    2122.7
    (906.19)
    1537.4
    (448.23)
    1648.8
    (713.36)
    2089.7
    (800.79)
    1873.9
    (552.78)
    1654.8
    (580.26)
    1948.8
    (418.21)
    PVR: Change at hour 1
    60.2
    (377.48)
    -82.9
    (158.83)
    -24.2
    (165.45)
    -182.4
    (306.17)
    -147.1
    (360.44)
    -138.4
    (85.91)
    67.9
    (256.27)
    SVR: Change at hour 1
    -125.0
    (439.77)
    -174.7
    (231.65)
    -139.0
    (526.65)
    -371.3
    (678.24)
    -373.1
    (461.11)
    -39.1
    (128.88)
    63.9
    (352.95)
    PVR: Change at hour 2
    -19.8
    (316.70)
    -112.5
    (129.43)
    -6.5
    (132.03)
    -114.0
    (487.12)
    -196.7
    (264.20)
    -194.4
    (207.82)
    142.8
    (509.00)
    SVR: Change at hour 2
    -281.4
    (252.62)
    -194.2
    (296.66)
    -173.7
    (382.66)
    -238.7
    (715.18)
    -538.9
    (327.15)
    -206.3
    (208.43)
    12.7
    (551.13)
    PVR: Change at hour 3
    0.9
    (292.22)
    -8.4
    (112.08)
    -3.2
    (173.46)
    -215.6
    (549.52)
    -153.9
    (254.82)
    -150.7
    (272.64)
    223.3
    (488.72)
    SVR: Change at hour 3
    -269.3
    (256.20)
    -66.6
    (189.66)
    -93.8
    (389.95)
    -337.2
    (935.47)
    -432.3
    (298.78)
    -233.7
    (272.19)
    30.9
    (487.52)
    PVR: Change at hour 4
    -28.9
    (236.91)
    -81.7
    (127.73)
    10.5
    (187.79)
    -247.4
    (281.78)
    -188.5
    (280.24)
    -133.6
    (219.26)
    260.9
    (574.22)
    SVR: Change at hour 4
    -385.7
    (290.25)
    -53.2
    (185.94)
    -117.8
    (412.25)
    -505.2
    (731.80)
    -353.9
    (403.12)
    -215.6
    (272.13)
    92.3
    (517.94)
    10. Secondary Outcome
    Title Mean Change From Baseline in Heart Rate (HR) at Hour 1, 2, 3 and 4 Post Dose
    Description Hourly changes from baseline in HR were reported.
    Time Frame Baseline, 1, 2, 3, 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    FAS included all randomized participants who received study medication.
    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1.
    Measure Participants 6 6 7 6 6 7 6
    Baseline
    78.2
    (13.21)
    85.3
    (16.28)
    90.1
    (17.10)
    75.5
    (14.05)
    77.2
    (15.94)
    91.9
    (17.90)
    86.7
    (19.43)
    Change at hour 1
    -0.3
    (11.60)
    -3.5
    (5.50)
    -1.1
    (5.01)
    4.3
    (11.17)
    6.8
    (7.31)
    -0.9
    (6.09)
    -2.7
    (6.47)
    Change at hour 2
    -0.5
    (8.14)
    -2.8
    (3.60)
    0.1
    (5.52)
    4.2
    (9.37)
    9.7
    (8.02)
    -2.3
    (4.75)
    -0.5
    (6.12)
    Change at hour 3
    -1.0
    (10.39)
    -1.2
    (3.19)
    -3.3
    (9.66)
    -1.8
    (7.05)
    10.2
    (4.12)
    -3.1
    (7.99)
    -0.8
    (6.82)
    Change at hour 4
    1.5
    (8.17)
    -3.3
    (2.80)
    -2.0
    (11.17)
    6.0
    (8.34)
    5.7
    (4.32)
    -6.1
    (6.72)
    -0.5
    (8.60)
    11. Secondary Outcome
    Title Number of Participants With Clinically Significant Laboratory Values
    Description Criteria for clinically significant laboratory values:hemoglobin, hematocrit and red blood cells(less than[<]0.8*lower limit of normal[LLN]); leucocytes (<0.6*LLN/greater than[>]1.5*upper limit of normal[ULN]);platelets (<0.5*LLN></0>1.75* ULN);neutrophils, lymphocytes(<0.8*LLN></0>1.2* ULN); eosinophils, basophils, monocytes (>1.2*ULN);bilirubin (>1.5*ULN);aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase(>3*ULN);creatinine, blood urea nitrogen (>1.3*ULN);glucose(<0.6*LLN></0>1.5* ULN); uric acid(>1.2*ULN);sodium(<0.95*LLN></0>1.05*ULN); potassium, chloride, calcium(<0.9*LLN></0>1.1* ULN); albumin, total protein(<0.8></0>1.2* ULN); creatine kinase(>2.0*ULN);urine red blood cells(RBCs), urine white blood cells(WBCs)(>=6 per high-powered field);qualitative urine glucose, urine ketones, urine protein, urine blood/hemoglobin(>=1); urine bacteria(>20 per high-powered field); pregnancy test, urine protein, quantitative random serum pregnancy test (>=1).
    Time Frame Baseline up-to follow up (Day 3 to 5)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all randomized participants who received study medication.
    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1.
    Measure Participants 6 6 7 6 6 7 6
    Count of Participants [Participants]
    3
    50%
    3
    50%
    3
    42.9%
    3
    50%
    3
    50%
    3
    42.9%
    3
    50%
    12. Secondary Outcome
    Title Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Values
    Description Criteria for clinically significant changes (changes of potential clinical concern) in ECG parameters: increase from baseline of >=30 to <60 milliseconds (msec) or >=60 msec in corrected QT interval (QTc), QT interval corrected using Fridericia's correction (QTcF) and QT interval corrected using Bazett's correction (QTcB); Increase from baseline of >= 25% (when baseline was >200 msec) or increase from baseline of >=50% (when baseline was <=200 msec) in PR interval; and Increase from baseline of >= 25% (when baseline was >100 msec) or increase from baseline of >=50% (when baseline was <=100 msec) in QRS interval. Number of participants with any clinically significant change in ECG values were reported.
    Time Frame Baseline up-to follow up (Day 3 to 5)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all randomized participants who received study medication.
    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1.
    Measure Participants 6 6 7 6 6 7 6
    Count of Participants [Participants]
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    13. Secondary Outcome
    Title Change From Baseline in Mean Partial Pressure of Oxygen (PaO2) and Carbon Dioxide (PaCO2) at Hour 1 and 4 Post Dose
    Description Arterial blood samples for PaO2 and PaCO2 collected via an arterial line were assessed. PaO2 is the measure of oxygen level in the arterial blood and PaCO2 is the measure of carbon dioxide level in the arterial blood.
    Time Frame Baseline; 1, 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all randomized participants who received study medication. Here, N (overall number of participants analyzed) = participants evaluable for this measure and 'Number Analyzed' = participants who were evaluable at given time points for each group.
    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1.
    Measure Participants 6 5 7 5 6 6 6
    PaO2: Baseline
    64.1
    (9.47)
    63.0
    (14.92)
    65.4
    (16.98)
    82.0
    (16.32)
    72.4
    (25.85)
    73.2
    (15.75)
    64.9
    (9.78)
    PaCO2: Baseline
    32.8
    (4.79)
    32.0
    (6.71)
    38.7
    (7.53)
    31.4
    (4.83)
    36.3
    (6.09)
    39.3
    (10.75)
    41.6
    (15.07)
    PaO2: Change at Hour 1
    -1.4
    (11.06)
    -4.4
    (6.22)
    -0.6
    (7.98)
    -6.5
    (12.16)
    -10.8
    (12.99)
    -13.7
    (11.17)
    2.4
    (12.48)
    PaCO2: Change at Hour 1
    0.5
    (2.69)
    1.4
    (1.96)
    -0.7
    (3.70)
    -0.2
    (3.62)
    -2.1
    (2.98)
    1.4
    (4.26)
    -1.4
    (3.77)
    PaO2: Change at Hour 4
    0.8
    (8.03)
    -0.4
    (4.04)
    0.3
    (13.47)
    -4.0
    (8.39)
    -10.3
    (9.65)
    -7.7
    (15.61)
    3.6
    (7.47)
    PaCO2: Change at Hour 4
    -0.7
    (1.36)
    1.0
    (2.48)
    -1.9
    (4.44)
    -1.6
    (3.59)
    -3.3
    (2.91)
    0.6
    (3.68)
    0.8
    (10.55)
    14. Secondary Outcome
    Title Plasma Concentration of PF-00489791 and Sildenafil
    Description
    Time Frame 1, 2, 3, 4, 5, 6, 8 hours post-dose on Day 1, follow up (Day 3 to 5)

    Outcome Measure Data

    Analysis Population Description
    Data was not reported for this outcome measure because the study was terminated and as per change in planned analysis, the pharmacokinetic parameters were not to be summarized.
    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1.
    Measure Participants 0 0 0 0 0 0 0

    Adverse Events

    Time Frame
    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 participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Safety population.
    Arm/Group Title Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Arm/Group Description Single oral dose of 2 placebo matched to PF-00489791 tablet along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 1 milligram (mg) tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 2 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 2 mg tablet (equivalent to PF-00489791 4 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 PF-00489791 10 mg tablet along with 1 placebo matched to PF-00489791 tablet and 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 2 PF-00489791 10 mg tablet (equivalent to PF-00489791 20 mg) along with 1 placebo matched to sildenafil tablet on Day 1. Single oral dose of 1 sildenafil 20 mg tablet along with 2 placebo matched to PF-00489791 tablet on Day 1.
    All Cause Mortality
    Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/6 (33.3%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 1/7 (14.3%) 0/6 (0%)
    Cardiac disorders
    Cardiac failure congestive 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 1/7 (14.3%) 0/6 (0%)
    Gastrointestinal disorders
    Haemorrhoids 1/6 (16.7%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    General disorders
    Chest pain 1/6 (16.7%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Oedema peripheral 1/6 (16.7%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Vulval cancer 0/5 (0%) 0/5 (0%) 0/4 (0%) 0/4 (0%) 0/3 (0%) 1/5 (20%) 0/4 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo PF-00489791 1 mg PF-00489791 2 mg PF-00489791 4 mg PF-00489791 10 mg PF-00489791 20 mg Sildenafil
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/6 (33.3%) 4/6 (66.7%) 2/7 (28.6%) 5/6 (83.3%) 4/6 (66.7%) 2/7 (28.6%) 3/6 (50%)
    Blood and lymphatic system disorders
    Eosinophilia 1/6 (16.7%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Cardiac disorders
    Tachycardia 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Ventricular extrasystoles 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Eye disorders
    Eye irritation 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Ocular hyperaemia 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Gastrointestinal disorders
    Abdominal pain upper 0/6 (0%) 0/6 (0%) 1/7 (14.3%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Diarrhoea 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Nausea 1/6 (16.7%) 2/6 (33.3%) 0/7 (0%) 1/6 (16.7%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Vomiting 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 1/6 (16.7%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    General disorders
    Asthenia 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Axillary pain 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Chest discomfort 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Chest pain 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%)
    Oedema 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Pyrexia 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%)
    Hepatobiliary disorders
    Hyperbilirubinaemia 1/6 (16.7%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Infections and infestations
    Upper respiratory tract infection 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Urinary tract infection 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%)
    Investigations
    Alanine aminotransferase increased 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%)
    Aspartate aminotransferase increased 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%)
    Bacterial test positive 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Bilirubin conjugated increased 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Blood bilirubin increased 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%)
    Blood bilirubin unconjugated increased 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Blood creatinine increased 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%)
    Blood glucose increased 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%)
    Blood urea increased 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%)
    Blood uric acid increased 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%)
    Electrocardiogram QT prolonged 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Liver function test abnormal 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Oxygen saturation decreased 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Urinary sediment present 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Metabolism and nutrition disorders
    Hyperglycaemia 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 1/7 (14.3%) 0/6 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Nervous system disorders
    Dysgeusia 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Headache 0/6 (0%) 0/6 (0%) 0/7 (0%) 2/6 (33.3%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Syncope 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%)
    Tension headache 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Psychiatric disorders
    Anxiety 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Sleep disorder 0/6 (0%) 0/6 (0%) 0/7 (0%) 1/6 (16.7%) 0/6 (0%) 0/7 (0%) 0/6 (0%)
    Renal and urinary disorders
    Proteinuria 0/6 (0%) 0/6 (0%) 1/7 (14.3%) 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Respiratory, thoracic and mediastinal disorders
    Tachypnoea 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Skin and subcutaneous tissue disorders
    Dry skin 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Vascular disorders
    Haematoma 0/6 (0%) 0/6 (0%) 0/7 (0%) 2/6 (33.3%) 0/6 (0%) 1/7 (14.3%) 0/6 (0%)
    Hot flush 0/6 (0%) 0/6 (0%) 0/7 (0%) 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)
    Hypotension 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%) 1/6 (16.7%) 0/7 (0%) 0/6 (0%)

    Limitations/Caveats

    Study was terminated prematurely as further continuation would not have meaningfully contributed to the next phase of development.

    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.

    Results Point of Contact

    Name/Title Pfizer ClinicalTrials.gov Call Center
    Organization Pfizer, Inc.
    Phone 1-800-718-1021
    Email ClinicalTrials.gov_Inquiries@pfizer.com
    Responsible Party:
    Pfizer
    ClinicalTrials.gov Identifier:
    NCT00853112
    Other Study ID Numbers:
    • A7331009
    • 2008-003572-21
    First Posted:
    Mar 2, 2009
    Last Update Posted:
    Oct 24, 2017
    Last Verified:
    Sep 1, 2017