Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1) (ATHENA-1)

Measure Type	Primary
Measure Title	Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF)
Measure Description	The primary objective of this study is to evaluate the change from baseline in PVR, and other hemodynamic parameters, following the addition of ambrisentan to background PDE-5i therapy in subjects with PAH who have demonstrated a sub-optimal response to PDE-5i monotherapy. A decrease in measurement value (dynes sec/cm^5) indicates improvement for this patient population.
Time Frame	Baseline to Week 24

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients with measurements at Baseline and Week 24 were evaluated

Reporting Groups

	Description
Ambrisentan Only	Patients were assigned ambrisentan at open-label enrollment or randomization, and received at least one dose of ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor (PDE-5i) (33 patients had baseline measurements in this group)
Placebo/Ambrisentan	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i; patients also received at least one dose of open-label ambrisentan plus an approved PDE-5i (4 patients had baseline measurements in this group)
Placebo Only	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i and did not receive ambrisentan (1 patient had baseline measurements in this group)
Any Ambrisentan	Patients were assigned either ambrisentan or placebo at enrollment or randomization and received at least one dose of ambrisentan plus an approved PDE-5i (37 patients had baseline measurements in this group)
Any Placebo	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i (5 patients had baseline measurements in this group)

Measured Values

	Ambrisentan Only	Placebo/Ambrisentan	Placebo Only	Any Ambrisentan	Any Placebo
Participants Analyzed  [Units: Participants]	31	4	0	35	4
Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF)  [Units: Dynes sec/cm^5] Mean (Standard Deviation)
Baseline	761.2  (306.57)	731.6  (278.02)		758.0  (300.12)	703.6  (248.73)
Week 24	518.8  (196.35)	439.8  (130.34)		509.8  (190.18)	439.8  (130.34)

Statistical Analysis 1 for Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF)
Statistical Analysis 2 for Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF)
Statistical Analysis 3 for Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF)
Statistical Analysis 4 for Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF)

Measure Type	Secondary
Measure Title	Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF)
Measure Description	This secondary hemodynamic outcome is supportive of the primary outcome. A decrease in measurement value (mmHg) indicates improvement for this patient population.
Time Frame	Baseline to Week 24

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients with measurements at Baseline and Week 24 were evaluated

Reporting Groups

	Description
Ambrisentan Only	Patients were assigned ambrisentan at open-label enrollment or randomization, and received at least one dose of ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor (PDE-5i) (33 patients had baseline measurements in this group)
Placebo/Ambrisentan	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i; patients also received at least one dose of open-label ambrisentan plus an approved PDE-5i (4 patients had baseline measurements in this group)
Placebo Only	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i and did not receive ambrisentan (1 patient had baseline measurements in this group)
Any Ambrisentan	Patients were assigned either ambrisentan or placebo at enrollment or randomization and received at least one dose of ambrisentan plus an approved PDE-5i (37 patients had baseline measurements in this group)
Any Placebo	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i (5 patients had baseline measurements in this group)

Measured Values

	Ambrisentan Only	Placebo/Ambrisentan	Placebo Only	Any Ambrisentan	Any Placebo
Participants Analyzed  [Units: Participants]	31	4	0	35	4
Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF)  [Units: mmHg] Mean (Standard Deviation)
Baseline	49.9  (9.75)	54.5  (12.50)		50.4  (9.98)	52.8  (11.48)
Week 24	44.4  (10.95)	38.8  (9.60)		43.8  (10.83)	38.8  (9.60)

Statistical Analysis 1 for Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF)
Statistical Analysis 2 for Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF)
Statistical Analysis 3 for Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF)
Statistical Analysis 4 for Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF)

Measure Type	Secondary
Measure Title	Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF)
Measure Description	This secondary hemodynamic outcome is supportive of the primary outcome. A decrease in measurement value (mmHg) indicates improvement for this patient population.
Time Frame	Baseline to Week 24

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients with measurements at Baseline and Week 24 were evaluated

Reporting Groups

	Description
Ambrisentan Only	Patients were assigned ambrisentan at open-label enrollment or randomization, and received at least one dose of ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor (PDE-5i) (33 patients had baseline measurements in this group)
Placebo/Ambrisentan	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i; patients also received at least one dose of open-label ambrisentan plus an approved PDE-5i (4 patients had baseline measurements in this group)
Placebo Only	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i and did not receive ambrisentan (1 patient had baseline measurements in this group)
Any Ambrisentan	Patients were assigned either ambrisentan or placebo at enrollment or randomization and received at least one dose of ambrisentan plus an approved PDE-5i (37 patients had baseline measurements in this group)
Any Placebo	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i (5 patients had baseline measurements in this group)

Measured Values

	Ambrisentan Only	Placebo/Ambrisentan	Placebo Only	Any Ambrisentan	Any Placebo
Participants Analyzed  [Units: Participants]	31	4	0	35	4
Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF)  [Units: mmHg] Mean (Standard Deviation)
Baseline	8.5  (4.82)	10.3  (2.63)		8.7  (4.64)	11.1  (2.97)
Week 24	8.4  (4.88)	6.3  (1.71)		8.1  (4.66)	6.3  (1.71)

Statistical Analysis 1 for Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF)
Statistical Analysis 2 for Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF)
Statistical Analysis 3 for Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF)
Statistical Analysis 4 for Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF)

Measure Type	Secondary
Measure Title	Change From Baseline in Cardiac Output (LOCF)
Measure Description	This secondary hemodynamic outcome is supportive of the primary outcome. An increase in measurement value (L/min) indicates improvement for this patient population.
Time Frame	Baseline to Week 24

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Patients with measurements at Baseline and Week 24 were evaluated

Reporting Groups

	Description
Ambrisentan Only	Patients were assigned ambrisentan at open-label enrollment or randomization, and received at least one dose of ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor (PDE-5i) (33 patients had baseline measurements in this group)
Placebo/Ambrisentan	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i; patients also received at least one dose of open-label ambrisentan plus an approved PDE-5i (4 patients had baseline measurements in this group)
Placebo Only	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i and did not receive ambrisentan (1 patient had baseline measurements in this group)
Any Ambrisentan	Patients were assigned either ambrisentan or placebo at enrollment or randomization and received at least one dose of ambrisentan plus an approved PDE-5i (37 patients had baseline measurements in this group)
Any Placebo	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i (5 patients had baseline measurements in this group)

Measured Values

	Ambrisentan Only	Placebo/Ambrisentan	Placebo Only	Any Ambrisentan	Any Placebo
Participants Analyzed  [Units: Participants]	28	4	0	32	4
Change From Baseline in Cardiac Output (LOCF)  [Units: L/min] Mean (Standard Deviation)
Baseline	4.4  (1.22)	4.8  (0.81)		4.4  (1.17)	4.8  (0.71)
Week 24	5.2  (1.27)	5.2  (1.22)		5.2  (1.24)	5.2  (1.22)

Statistical Analysis 1 for Change From Baseline in Cardiac Output (LOCF)
Statistical Analysis 2 for Change From Baseline in Cardiac Output (LOCF)
Statistical Analysis 3 for Change From Baseline in Cardiac Output (LOCF)
Statistical Analysis 4 for Change From Baseline in Cardiac Output (LOCF)

Measure Type	Secondary
Measure Title	Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Measure Description	The primary analysis of this secondary outcome measure is mean change from Baseline to Week 24. The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated. An increase in measurement value (meters walked) indicates improvement for this patient population.
Time Frame	Baseline to Week 48

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All enrolled Population

Reporting Groups

	Description
Ambrisentan Only	Patients were assigned ambrisentan at open-label enrollment or randomization, and received at least one dose of ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor (PDE-5i) (33 patients had baseline measurements in this group)
Placebo/Ambrisentan	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i; patients also received at least one dose of open-label ambrisentan plus an approved PDE-5i (4 patients had baseline measurements in this group)
Placebo Only	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i and did not receive ambrisentan (1 patient had baseline measurements in this group)
Any Ambrisentan	Patients were assigned either ambrisentan or placebo at enrollment or randomization and received at least one dose of ambrisentan plus an approved PDE-5i (37 patients had baseline measurements in this group)
Any Placebo	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i (5 patients had baseline measurements in this group)

Measured Values

	Ambrisentan Only	Placebo/Ambrisentan	Placebo Only	Any Ambrisentan	Any Placebo
Participants Analyzed  [Units: Participants]	33	4	1	37	5
Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)  [Units: Meters walked] Mean (Standard Deviation)
Baseline	361.9  (98.74)	433.3  (80.77)	335.0  (0.0)	369.6  (98.56)	413.6  (82.61)
Week 4	376.5  (106.08)	441.0  (83.88)	442.0  (0.0)	383.7  (104.85)	441.2  (72.65)
Week 12	377.9  (109.61)	435.8  (134.61)	422.0  (0.0)	384.3  (111.96)	433.0  (116.74)
Week 24	382.4  (104.96)	423.8  (110.05)	422.0  (0.0)	387.0  (104.73)	423.4  (95.31)
Week 36	366.5  (127.62)	399.3  (152.93)	402.0  (0.0)	370.2  (128.61)	399.8  (132.45)
Week 48	378.9  (124.18)	383.5  (192.47)	402.0  (0.0)	379.4  (129.75)	387.2  (166.89)

Statistical Analysis 1 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 2 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 3 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 4 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 5 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 6 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 7 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 8 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 9 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 10 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 11 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 12 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 13 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 14 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 15 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 16 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 17 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 18 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 19 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 20 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 21 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 22 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 23 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 24 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 25 for Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)

Measure Type	Secondary
Measure Title	Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Measure Description	The primary analysis of this secondary outcome measure is mean change from Baseline to Week 24. The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated. The dyspnea index measures the degree of breathlessness after completion of the 6MWT using a scale of 0 to 10, with 0 indicating no breathlessness and 10 indicating maximum breathlessness.
Time Frame	Baseline to Week 48

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All enrolled Population

Reporting Groups

	Description
Ambrisentan Only	Patients were assigned ambrisentan at open-label enrollment or randomization, and received at least one dose of ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor (PDE-5i) (33 patients had baseline measurements in this group)
Placebo/Ambrisentan	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i; patients also received at least one dose of open-label ambrisentan plus an approved PDE-5i (4 patients had baseline measurements in this group)
Placebo Only	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i and did not receive ambrisentan (1 patient had baseline measurements in this group)
Any Ambrisentan	Patients were assigned either ambrisentan or placebo at enrollment or randomization and received at least one dose of ambrisentan plus an approved PDE-5i (37 patients had baseline measurements in this group)
Any Placebo	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i (5 patients had baseline measurements in this group)

Measured Values

	Ambrisentan Only	Placebo/Ambrisentan	Placebo Only	Any Ambrisentan	Any Placebo
Participants Analyzed  [Units: Participants]	33	4	1	37	5
Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)  [Units: Units on a scale] Mean (Standard Deviation)
Baseline	3.7  (2.07)	2.5  (1.29)	3.0  (0.0)	3.6  (2.03)	2.6  (1.14)
Week 4	3.2  (1.68)	3.3  (2.22)	2.0  (0.0)	3.2  (1.71)	3.0  (2.00)
Week 12	3.2  (1.94)	4.0  (2.83)	3.0  (0.0)	3.3  (2.02)	3.8  (2.49)
Week 24	2.9  (1.96)	1.9  (1.31)	3.0  (0.0)	2.8  (1.91)	2.1  (1.24)
Week 36	3.2  (2.29)	3.5  (2.65)	3.0  (0.0)	3.2  (2.29)	3.4  (2.30)
Week 48	3.1  (2.32)	3.5  (4.04)	3.0  (0.0)	3.1  (2.49)	3.4  (3.51)

Statistical Analysis 1 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 2 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 3 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 4 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 5 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 6 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 7 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 8 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 9 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 10 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 11 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 12 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 13 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 14 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 15 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 16 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 17 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 18 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 19 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 20 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 21 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 22 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 23 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 24 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 25 for Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)

Measure Type	Secondary
Measure Title	Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Measure Description	The primary analysis of this secondary outcome measure is mean change from Baseline to Week 24. The changes from Baseline to Weeks 12, 36, and 48 were also evaluated. Lower scores and decreases from baseline represent improved functioning and QOL. The CAMPHOR survey was not assessed at Week 4. The total CAMPHOR score scale ranges from 0 (good) to 25 (poor). A reduction in score over time represents improvement in this patient population.
Time Frame	Baseline to Week 48

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All enrolled Population

Reporting Groups

	Description
Ambrisentan Only	Patients were assigned ambrisentan at open-label enrollment or randomization, and received at least one dose of ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor (PDE-5i) (33 patients had baseline measurements in this group)
Placebo/Ambrisentan	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i; patients also received at least one dose of open-label ambrisentan plus an approved PDE-5i (4 patients had baseline measurements in this group)
Placebo Only	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i and did not receive ambrisentan (1 patient had baseline measurements in this group)
Any Ambrisentan	Patients were assigned either ambrisentan or placebo at enrollment or randomization and received at least one dose of ambrisentan plus an approved PDE-5i (37 patients had baseline measurements in this group)
Any Placebo	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i (5 patients had baseline measurements in this group)

Measured Values

	Ambrisentan Only	Placebo/Ambrisentan	Placebo Only	Any Ambrisentan	Any Placebo
Participants Analyzed  [Units: Participants]	33	4	1	37	5
Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)  [Units: Units on a scale] Mean (Standard Deviation)
Baseline	8.2  (6.14)	4.3  (5.44)	4.0  (0.0)	7.7  (6.12)	4.2  (4.71)
Week 12	6.8  (5.59)	5.5  (3.11)	2.0  (0.0)	6.7  (5.32)	4.8  (3.11)
Week 24	7.2  (5.82)	3.0  (2.94)	2.0  (0.0)	6.7  (5.69)	2.8  (2.59)
Week 36	7.7  (6.10)	3.5  (3.70)	3.0  (0.0)	7.2  (5.98)	3.4  (3.21)
Week48	7.6  (6.87)	3.8  (3.50)	3.0  (0.0)	7.1  (6.63)	3.6  (3.05)

Statistical Analysis 1 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 2 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 3 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 4 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 5 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 6 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 7 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 8 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 9 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 10 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 11 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 12 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 13 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 14 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 15 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 16 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 17 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 18 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 19 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Statistical Analysis 20 for Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)

Measure Type	Secondary
Measure Title	Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48.
Measure Description	The primary analysis of this secondary outcome measure is change from Baseline to Week 24. The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated. WHO categories are 1 to 4 with the worst category being 4. Improvement is represented by a change in category to a lower number (for example, change from category 3 to 2), and deterioration is represented by a change in category to a higher number (for example, change from category 2 to 4). No change is represented by no change in category (for example, category 2 which remains 2).
Time Frame	Baseline to Week 48

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All enrolled Population

Reporting Groups

	Description
Ambrisentan Only	Patients were assigned ambrisentan at open-label enrollment or randomization, and received at least one dose of ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor (PDE-5i) (33 patients had baseline measurements in this group)
Placebo/Ambrisentan	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i; patients also received at least one dose of open-label ambrisentan plus an approved PDE-5i (4 patients had baseline measurements in this group)
Placebo Only	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i and did not receive ambrisentan (1 patient had baseline measurements in this group)
Any Ambrisentan	Patients were assigned either ambrisentan or placebo at enrollment or randomization and received at least one dose of ambrisentan plus an approved PDE-5i (37 patients had baseline measurements in this group)
Any Placebo	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i (5 patients had baseline measurements in this group)

Measured Values

	Ambrisentan Only	Placebo/Ambrisentan	Placebo Only	Any Ambrisentan	Any Placebo
Participants Analyzed  [Units: Participants]	33	4	1	37	5
Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48.  [Units: Participants]
Week 4 - Improvement	3	0	1	3	1
Week 4 - No Change	29	4	0	33	4
Week 4 - Deterioration	0	0	0	0	0
Week 4 - Missing Data	1	0	0	1	0
Week 12 - Improvement	8	1	1	9	2
Week 12 - No Change	24	3	0	27	3
Week 12 - Deterioration	0	0	0	0	0
Week 12 - Missing Data	1	0	0	1	0
Week 24 - Improvement	12	2	1	14	3
Week 24 - No Change	19	2	0	21	2
Week 24 - Deterioration	1	0	0	1	0
Week 24 - Missing Data	1	0	0	1	0
Week 36 - Improvement	17	2	1	19	3
Week 36 - No Change	14	2	0	16	2
Week 36 - Deterioration	1	0	0	1	0
Week 36 - Missing Data	1	0	0	1	0
Week 48 - Improvement	14	1	1	15	2
Week 48 - No Change	17	3	0	20	3
Week 48 - Deterioration	1	0	0	1	0
Week 48 - Missing Data	1	0	0	1	0

No statistical analysis provided for Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48.

Measure Type	Secondary
Measure Title	Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Measure Description	The primary analysis of this secondary outcome measure is mean percent change from Baseline to Week 24. The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated. A decrease in log-transformed measurement value (pg/mL) indicates improvement for this patient population.
Time Frame	Baseline to Week 48

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
One patient (Any Placebo) was not evaluated for NT-proBNP. One patient (Placebo Only) had no baseline measurement, so no statistical analyses for change from baseline are given for the placebo only group (patient was only subject in this group).

Reporting Groups

	Description
Ambrisentan Only	Patients were assigned ambrisentan at open-label enrollment or randomization, and received at least one dose of ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor (PDE-5i) (33 patients had baseline measurements in this group)
Placebo/Ambrisentan	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i; patients also received at least one dose of open-label ambrisentan plus an approved PDE-5i (4 patients had baseline measurements in this group)
Placebo Only	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i and did not receive ambrisentan (1 patient had baseline measurements in this group)
Any Ambrisentan	Patients were assigned either ambrisentan or placebo at enrollment or randomization and received at least one dose of ambrisentan plus an approved PDE-5i (37 patients had baseline measurements in this group)
Any Placebo	Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i (5 patients had baseline measurements in this group)

Measured Values

	Ambrisentan Only	Placebo/Ambrisentan	Placebo Only	Any Ambrisentan	Any Placebo
Participants Analyzed  [Units: Participants]	33	4	1	37	4
Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)  [Units: pg/mL (log-transformed)] Mean (Standard Deviation)
Baseline	6.1  (1.10)	6.7  (1.02)	0.0  (0.0)	6.2  (1.10)	6.7  (1.02)
Week 4	5.7  (1.02)	6.2  (1.80)	7.5  (0.0)	5.7  (1.05)	6.7  (1.46)
Week 12	5.7  (1.01)	6.3  (0.45)	7.6  (0.0)	5.8  (0.99)	6.8  (0.80)
Week 24	5.7  (1.03)	6.0  (0.98)	7.6  (0.0)	5.7  (1.02)	6.4  (1.12)
Week 36	5.7  (1.19)	5.9  (0.64)	8.0  (0.0)	5.7  (1.14)	6.3  (1.08)
Week 48	5.6  (1.16)	6.4  (0.82)	8.0  (0.0)	5.7  (1.14)	6.7  (1.01)

Statistical Analysis 1 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 2 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 3 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 4 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 5 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 6 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 7 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 8 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 9 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 10 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 11 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 12 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 13 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 14 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 15 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 16 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 17 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 18 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 19 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Statistical Analysis 20 for Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)

Measure Type	Secondary
Measure Title	Time to Clinical Worsening of PAH, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48
Measure Description	The time to clinical worsening was defined as the time from enrollment to the first occurrence of death, lung transplantation, hospitalization for PAH, atrial septostomy, or initiation of chronic parenteral prostanoid therapy. Results are presented as the Kaplan-Meier estimate (% probability) of having clinical worsening after a given time.
Time Frame	Baseline to Week 48+

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Ambrisentan Only and Any Ambrisentan Groups were analyzed for Time to Clinical Worsening

Reporting Groups

	Description
Ambrisentan Only	Patients were assigned ambrisentan at open-label enrollment or randomization, and received at least one dose of ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor (PDE-5i) (33 patients had baseline measurements in this group)
Any Ambrisentan	Patients were assigned either ambrisentan or placebo at enrollment or randomization and received at least one dose of ambrisentan plus an approved PDE-5i (37 patients had baseline measurements in this group)

Measured Values

	Ambrisentan Only	Any Ambrisentan
Participants Analyzed  [Units: Participants]	33	37
Time to Clinical Worsening of PAH, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48  [Units: Probability of clinical worsening (%)] Number (95% Confidence Interval)
At Week 4	0   (0.0 to 0.0)	0   (0.0 to 0.0)
At Week 8	0   (0.0 to 0.0)	0   (0.0 to 0.0)
At Week 12	0   (0.0 to 0.0)	0   (0.0 to 0.0)
At Week 16	0   (0.0 to 0.0)	0   (0.0 to 0.0)
At Week 20	3   (0.0 to 9.1)	3   (0.0 to 8.2)
At Week 24	3   (0.0 to 9.1)	3   (0.0 to 8.2)
At Week 28	6   (0.0 to 14.7)	6   (0.0 to 13.1)
At Week 32	16   (3.1 to 29.1)	14   (2.7 to 25.9)
At Week 36	16   (3.1 to 29.1)	14   (2.7 to 25.9)
At Week 40	20   (5.6 to 34.0)	17   (4.7 to 30.1)
At Week 44	20   (5.6 to 34.0)	17   (4.7 to 30.1)
At Week 48	20   (5.6 to 34.0)	17   (4.7 to 30.1)
After Week 48	20   (5.6 to 34.0)	17   (4.7 to 30.1)

No statistical analysis provided for Time to Clinical Worsening of PAH, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48

Measure Type	Secondary
Measure Title	Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48
Measure Description	Overall survival was defined as the time from initiation of active treatment to death. Results are presented as the Kaplan-Meier estimate (% probability) of death after a given time.
Time Frame	Baseline to Week 48+

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The Ambrisentan Only and Any Ambrisentan Groups were analyzed for Overall Survival

Reporting Groups

	Description
Ambrisentan Only	Patients were assigned ambrisentan at open-label enrollment or randomization, and received at least one dose of ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor (PDE-5i) (33 patients had baseline measurements in this group)
Any Ambrisentan	Patients were assigned either ambrisentan or placebo at enrollment or randomization and received at least one dose of ambrisentan plus an approved PDE-5i (37 patients had baseline measurements in this group)

Measured Values

	Ambrisentan Only	Any Ambrisentan
Participants Analyzed  [Units: Participants]	33	37
Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48  [Units: Probability of death occurring (%)] Number (95% Confidence Interval)
At Week 4	0   (0.0 to 0.0)	0   (0.0 to 0.0)
At Week 8	0   (0.0 to 0.0)	0   (0.0 to 0.0)
At Week 12	0   (0.0 to 0.0)	0   (0.0 to 0.0)
At Week 16	0   (0.0 to 0.0)	0   (0.0 to 0.0)
At Week 20	0   (0.0 to 0.0)	0   (0.0 to 0.0)
At Week 24	0   (0.0 to 0.0)	0   (0.0 to 0.0)
At Week 28	0   (0.0 to 0.0)	0   (0.0 to 0.0)
At Week 32	0   (0.0 to 0.0)	0   (0.0 to 0.0)
At Week 36	0   (0.0 to 0.0)	0   (0.0 to 0.0)
At Week 40	4   (0.0 to 10.8)	3   (0.0 to 9.4)
At Week 44	4   (0.0 to 10.8)	3   (0.0 to 9.4)
At Week 48	4   (0.0 to 10.8)	3   (0.0 to 9.4)
After Week 48	4   (0.0 to 10.8)	3   (0.0 to 9.4)

No statistical analysis provided for Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48