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

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

Population: 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.

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

Population: 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.

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

Population: 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.

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

Population: FAS included all randomized participants who received study medication. Here, 'Number Analyzed' = participants who were evaluable at given time points for each group.

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

Population: FAS included all randomized participants who received study medication. Here, 'Number Analyzed' = participants who were evaluable at given time points for each group.

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

Population: 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.

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

Population: 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.

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

Population: 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.

Hourly changes from baseline in HR were reported.

Time frame: Baseline, 1, 2, 3, 4 hours post-dose on Day 1

Population: FAS included all randomized participants who received study medication.

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

Population: FAS included all randomized participants who received study medication. Here, 'Number Analyzed' = participants who were evaluable at given time points for each group.

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

Population: FAS included all randomized participants who received study medication. Here, N (overall number of participants analyzed) = participants evaluable for this measure.

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)

Population: Safety analysis set included all randomized participants who received study medication.

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)

Population: Safety analysis set included all randomized participants who received study medication.

Time frame: 1, 2, 3, 4, 5, 6, 8 hours post-dose on Day 1, follow up (Day 3 to 5)

Population: 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.