Evaluate the Efficacy, Safety and Pharmacokinetics of GSK1325760A in the Treatment of Pulmonary Arterial Hypertension

• Mean Change From Baseline in Six Minutes Walk Distance (6MWD) at Week 24/Withdrawal [ Time Frame: Baseline and Week 24/Withdrawal ] [ Designated as safety issue: No ]
  Change from baseline was calculated as the Week 24/Withdrawal value minus the basline value. 6MWD was measured by a 6 minute walk test. This test measures the distance that a subject can walk in a period of 6 minutes. Imputation technique was last observation carried forward.
• Mean Change From Baseline in the Borg Dyspnea Index (BDI) at Weeks 12 and 24 [ Time Frame: Baseline and Weeks 12 and 24 ] [ Designated as safety issue: No ]
  The BDI was calculated by using a 10-point scale (0 = None, 10 = Maximum). Change from baseline was calculated as the Week 12 and 24 values minus the baseline values. The BDI indicates the degree of breathlessness after completion of the 6 minute walk test. The BDI scale was assessed by each participant. Imputation technique was last observation carried forward.
• Number of Participants With a Change From Baseline in Their World Health Organization (WHO) Functional Classification (FC) at Weeks 12 and 24 [ Time Frame: Weeks 12 and 24 ] [ Designated as safety issue: No ]
  There are four grades for WHO FC (class I = none, Class IV = most severe). The WHO FC indicates the severity of Pulmonary Arterial Hypertension and is an adaptation of the New York Heart Association classification. It was assessed by the investigator. Imputation technique was last observation carried forward.
• Number of Participants With the Indicated Event, as an Assessment of Time to Clinical Worsening of Pulmonary Arterial Hypertension (PAH) at Week 24, Assessed as the First Occurrence of a Particular Event [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
  Time to clinical worsening is defined as the time from baseline to the first occurrence of death, lung transplantation, hospitalization for PAH treatment, atrial septostomy, or study discontinuation due to change to other PAH treatment. Time to clinical worsening is measured as the number of participants who experienced these events during 24 weeks.
• Mean Change From Baseline in Mean Pulmonary Atery Pressure (mPAP) and Mean Right Atrial Pressure (mRAP) at Weeks 12 and 24 [ Time Frame: Baseline and Weeks 12 and 24 ] [ Designated as safety issue: No ]
  mPAP and mRAP are measures of cardiopulmonary hemodynamics. Change from baseline was calculated as the Week 12 and 24 values minus the baseline value. Observed data analysis (no imputation techniques).
• Mean Change From Baseline in Cardiac Index (CI) at Weeks 12 and 24 [ Time Frame: Baseline and Weeks 12 and 24 ] [ Designated as safety issue: No ]
  CI is a measure of cardiopulmonary hemodynamics. Change from baseline was calculated as the Week 12 and 24 values minus the baseline value. Observed data analysis (no imputation techniques).
• Mean Change From Baseline in Cardiac Output (CO) at Weeks 12 and 24 [ Time Frame: Baseline and Weeks 12 and 24 ] [ Designated as safety issue: No ]
  CO is a measure of cardiopulmonary hemodynamics. Change from baseline was calculated as the Week 12 and 24 values minus the baseline value. Observed data analysis (no imputation techniques).
• Mean Change From Baseline in Pulmonary Vascular Resistance (PVR) at Weeks 12 and 24 [ Time Frame: Baseline and Weeks 12 and 24 ] [ Designated as safety issue: No ]
  PVR is a measure of cardiopulmonary hemodynamics. Change from baseline was calculated as the Week 12 and 24 values minus the baseline value. Observed data analysis (no imputation techniques).
• Mean Change From Baseline in B-type Natriuretic Peptide (BNP) Values at Weeks 12 and 24 [ Time Frame: Baseline and Weeks 12 and 24 ] [ Designated as safety issue: No ]
  Change from baseline was calculated as the Week 12 and 24 values minus the baseline value. BNP is a surrogate maker of heart failure and was measured by a central laboratory. Observed data analysis (no imputation techniques).

The primary objective of this study is to evaluate the effect of GSK1325760A on improvement in exercise capacity in subjects with pulmonary arterial hypertension (PAH).

The secondary objectives of this study are to evaluate administration of GSK1325760A on:

• The safety and tolerability
• Improvement of PAH
• The steady-state plasma pharmacokinetics of GSK1325760A

Inclusion criteria:

• Subjects must have a diagnosis of Pulmonary Arterial Hypertension (PAH) in clinical classification of Pulmonary Hypertension Group1
• The mean right heart catheterization parameters measured from 6 months prior to the administration of the investigational drug must meet the criteria below:
• Mean pulmonary arterial pressure (mPAP) of >25 mmHg
• Pulmonary vascular resistance (PVR) of >3 mmHg/L/min
• Mean pulmonary capillary wedge pressure or left ventricular end diastolic pressure of <15 mmHg (if measurable)
• The measured six minutes walk distance (6MWD) at screening visit is in the range of =>150m and <=450m