Trial Outcomes & Findings for Study of Add-on Ambrisentan Therapy to Background Phosphodiesterase Type-5 Inhibitor (PDE5i) Therapy in Pulmonary Arterial Hypertension (ATHENA-1) (NCT NCT00617305)

NCT ID: NCT00617305

Last Updated: 2012-07-30

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 38 participants
• Primary outcome timeframe: Baseline to Week 24
• Results posted on: 2012-07-30

Participant Flow

Patients were enrolled in 16 study sites in the US. The first patient was screened on 09 April 2008, and the last patient was enrolled on 28 July 2010. The last patient observation was on 25 July 2011. Originally a double-blind, placebo-controlled study, it was changed to open label on 12 June 2009 due to slow enrollment.

65 patients were screened; 8 were randomized (3 to ambrisentan and 5 to placebo) prior to study conversion to open label. The remaining patients were assigned to ambrisentan treatment.

Participant milestones

Measure	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)	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	Placebo Only Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i
Overall Study STARTED	33	4	1
Overall Study Completed 24-week Primary Analysis	31	4	0
Overall Study COMPLETED	25	4	0
Overall Study NOT COMPLETED	8	0	1

Reasons for withdrawal

Measure	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)	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	Placebo Only Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i
Overall Study Adverse Event	4	0	0
Overall Study Death	1	0	0
Overall Study Physician Decision	1	0	0
Overall Study Protocol Violation	1	0	1
Overall Study Withdrawal by Subject	1	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Ambrisentan Only n=33 Participants 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)	Placebo/Ambrisentan n=4 Participants 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	Placebo Only n=1 Participants Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i	Total n=38 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	29 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	34 Participants n=4 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Age Continuous	48.2 years STANDARD_DEVIATION 13.72 • n=5 Participants	43.5 years STANDARD_DEVIATION 14.89 • n=7 Participants	49.0 years STANDARD_DEVIATION 0 • n=5 Participants	47.8 years STANDARD_DEVIATION 13.52 • n=4 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	28 Participants n=4 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	10 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	8 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	8 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	25 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	30 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Race/Ethnicity, Customized Black or African American	2 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants
Race/Ethnicity, Customized Hispanic	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized More than one race	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized White	27 participants n=5 Participants	4 participants n=7 Participants	1 participants n=5 Participants	32 participants n=4 Participants
Region of Enrollment United States	33 participants n=5 Participants	4 participants n=7 Participants	1 participants n=5 Participants	38 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline to Week 24

Population: Patients with measurements at Baseline and Week 24 were evaluated

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.

Outcome measures

Measure	Ambrisentan Only n=31 Participants 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 n=4 Participants 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 n=35 Participants 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 n=4 Participants 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)
Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF) Baseline	761.2 dynes sec/cm^5 Standard Deviation 306.57	731.6 dynes sec/cm^5 Standard Deviation 278.02	—	758.0 dynes sec/cm^5 Standard Deviation 300.12	703.6 dynes sec/cm^5 Standard Deviation 248.73
Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF) Week 24	518.8 dynes sec/cm^5 Standard Deviation 196.35	439.8 dynes sec/cm^5 Standard Deviation 130.34	—	509.8 dynes sec/cm^5 Standard Deviation 190.18	439.8 dynes sec/cm^5 Standard Deviation 130.34

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Patients with measurements at Baseline and Week 24 were evaluated

This secondary hemodynamic outcome is supportive of the primary outcome. A decrease in measurement value (mmHg) indicates improvement for this patient population.

Outcome measures

Measure	Ambrisentan Only n=31 Participants 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 n=4 Participants 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 n=35 Participants 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 n=4 Participants 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)
Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF) Baseline	49.9 mmHg Standard Deviation 9.75	54.5 mmHg Standard Deviation 12.50	—	50.4 mmHg Standard Deviation 9.98	52.8 mmHg Standard Deviation 11.48
Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF) Week 24	44.4 mmHg Standard Deviation 10.95	38.8 mmHg Standard Deviation 9.60	—	43.8 mmHg Standard Deviation 10.83	38.8 mmHg Standard Deviation 9.60

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Patients with measurements at Baseline and Week 24 were evaluated

This secondary hemodynamic outcome is supportive of the primary outcome. A decrease in measurement value (mmHg) indicates improvement for this patient population.

Outcome measures

Measure	Ambrisentan Only n=31 Participants 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 n=4 Participants 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 n=35 Participants 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 n=4 Participants 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)
Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF) Baseline	8.5 mmHg Standard Deviation 4.82	10.3 mmHg Standard Deviation 2.63	—	8.7 mmHg Standard Deviation 4.64	11.1 mmHg Standard Deviation 2.97
Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF) Week 24	8.4 mmHg Standard Deviation 4.88	6.3 mmHg Standard Deviation 1.71	—	8.1 mmHg Standard Deviation 4.66	6.3 mmHg Standard Deviation 1.71

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Patients with measurements at Baseline and Week 24 were evaluated

This secondary hemodynamic outcome is supportive of the primary outcome. An increase in measurement value (L/min) indicates improvement for this patient population.

Outcome measures

Measure	Ambrisentan Only n=28 Participants 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 n=4 Participants 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 n=32 Participants 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 n=4 Participants 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)
Change From Baseline in Cardiac Output (LOCF) Baseline	4.4 L/min Standard Deviation 1.22	4.8 L/min Standard Deviation 0.81	—	4.4 L/min Standard Deviation 1.17	4.8 L/min Standard Deviation 0.71
Change From Baseline in Cardiac Output (LOCF) Week 24	5.2 L/min Standard Deviation 1.27	5.2 L/min Standard Deviation 1.22	—	5.2 L/min Standard Deviation 1.24	5.2 L/min Standard Deviation 1.22

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: All enrolled Population

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.

Outcome measures

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

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: All enrolled Population

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.

Outcome measures

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

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: All enrolled Population

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.

Outcome measures

Measure	Ambrisentan Only n=33 Participants 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 n=4 Participants 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 n=1 Participants 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 n=37 Participants 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 n=5 Participants 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)
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) Baseline	8.2 units on a scale Standard Deviation 6.14	4.3 units on a scale Standard Deviation 5.44	4.0 units on a scale Standard Deviation 0.0	7.7 units on a scale Standard Deviation 6.12	4.2 units on a scale Standard Deviation 4.71
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) Week 12	6.8 units on a scale Standard Deviation 5.59	5.5 units on a scale Standard Deviation 3.11	2.0 units on a scale Standard Deviation 0.0	6.7 units on a scale Standard Deviation 5.32	4.8 units on a scale Standard Deviation 3.11
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) Week 24	7.2 units on a scale Standard Deviation 5.82	3.0 units on a scale Standard Deviation 2.94	2.0 units on a scale Standard Deviation 0.0	6.7 units on a scale Standard Deviation 5.69	2.8 units on a scale Standard Deviation 2.59
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) Week 36	7.7 units on a scale Standard Deviation 6.10	3.5 units on a scale Standard Deviation 3.70	3.0 units on a scale Standard Deviation 0.0	7.2 units on a scale Standard Deviation 5.98	3.4 units on a scale Standard Deviation 3.21
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) Week48	7.6 units on a scale Standard Deviation 6.87	3.8 units on a scale Standard Deviation 3.50	3.0 units on a scale Standard Deviation 0.0	7.1 units on a scale Standard Deviation 6.63	3.6 units on a scale Standard Deviation 3.05

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: All enrolled Population

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).

Outcome measures

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

SECONDARY outcome

Timeframe: Baseline to Week 48

Population: 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).

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.

Outcome measures

Measure	Ambrisentan Only n=33 Participants 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 n=4 Participants 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 n=1 Participants 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 n=37 Participants 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 n=4 Participants 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)
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) Baseline	6.1 pg/mL (log-transformed) Standard Deviation 1.10 • Interval 19.62 to 43.89	6.7 pg/mL (log-transformed) Standard Deviation 1.02 • Interval -940.3 to 93.22	0.0 pg/mL (log-transformed) Standard Deviation 0.0	6.2 pg/mL (log-transformed) Standard Deviation 1.10 • Interval 19.3 to 42.62	6.7 pg/mL (log-transformed) Standard Deviation 1.02 • Interval -940.3 to 93.22
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) Week 4	5.7 pg/mL (log-transformed) Standard Deviation 1.02	6.2 pg/mL (log-transformed) Standard Deviation 1.80	7.5 pg/mL (log-transformed) Standard Deviation 0.0	5.7 pg/mL (log-transformed) Standard Deviation 1.05	6.7 pg/mL (log-transformed) Standard Deviation 1.46
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) Week 12	5.7 pg/mL (log-transformed) Standard Deviation 1.01	6.3 pg/mL (log-transformed) Standard Deviation 0.45	7.6 pg/mL (log-transformed) Standard Deviation 0.0	5.8 pg/mL (log-transformed) Standard Deviation 0.99	6.8 pg/mL (log-transformed) Standard Deviation 0.80
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) Week 24	5.7 pg/mL (log-transformed) Standard Deviation 1.03	6.0 pg/mL (log-transformed) Standard Deviation 0.98	7.6 pg/mL (log-transformed) Standard Deviation 0.0	5.7 pg/mL (log-transformed) Standard Deviation 1.02	6.4 pg/mL (log-transformed) Standard Deviation 1.12
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) Week 36	5.7 pg/mL (log-transformed) Standard Deviation 1.19	5.9 pg/mL (log-transformed) Standard Deviation 0.64	8.0 pg/mL (log-transformed) Standard Deviation 0.0	5.7 pg/mL (log-transformed) Standard Deviation 1.14	6.3 pg/mL (log-transformed) Standard Deviation 1.08
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) Week 48	5.6 pg/mL (log-transformed) Standard Deviation 1.16	6.4 pg/mL (log-transformed) Standard Deviation 0.82	8.0 pg/mL (log-transformed) Standard Deviation 0.0	5.7 pg/mL (log-transformed) Standard Deviation 1.14	6.7 pg/mL (log-transformed) Standard Deviation 1.01

SECONDARY outcome

Timeframe: Baseline to Week 48+

Population: The Ambrisentan Only and Any Ambrisentan Groups were analyzed for Time to Clinical Worsening

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.

Outcome measures

Measure	Ambrisentan Only n=33 Participants 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 n=37 Participants 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)
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 At Week 4	0 Probability of clinical worsening (%) Interval 0.0 to 0.0	0 Probability of clinical worsening (%) Interval 0.0 to 0.0	—	—	—
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 At Week 8	0 Probability of clinical worsening (%) Interval 0.0 to 0.0	0 Probability of clinical worsening (%) Interval 0.0 to 0.0	—	—	—
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 At Week 12	0 Probability of clinical worsening (%) Interval 0.0 to 0.0	0 Probability of clinical worsening (%) Interval 0.0 to 0.0	—	—	—
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 At Week 16	0 Probability of clinical worsening (%) Interval 0.0 to 0.0	0 Probability of clinical worsening (%) Interval 0.0 to 0.0	—	—	—
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 At Week 20	3 Probability of clinical worsening (%) Interval 0.0 to 9.1	3 Probability of clinical worsening (%) Interval 0.0 to 8.2	—	—	—
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 At Week 24	3 Probability of clinical worsening (%) Interval 0.0 to 9.1	3 Probability of clinical worsening (%) Interval 0.0 to 8.2	—	—	—
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 At Week 28	6 Probability of clinical worsening (%) Interval 0.0 to 14.7	6 Probability of clinical worsening (%) Interval 0.0 to 13.1	—	—	—
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 At Week 32	16 Probability of clinical worsening (%) Interval 3.1 to 29.1	14 Probability of clinical worsening (%) Interval 2.7 to 25.9	—	—	—
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 At Week 36	16 Probability of clinical worsening (%) Interval 3.1 to 29.1	14 Probability of clinical worsening (%) Interval 2.7 to 25.9	—	—	—
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 At Week 40	20 Probability of clinical worsening (%) Interval 5.6 to 34.0	17 Probability of clinical worsening (%) Interval 4.7 to 30.1	—	—	—
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 At Week 44	20 Probability of clinical worsening (%) Interval 5.6 to 34.0	17 Probability of clinical worsening (%) Interval 4.7 to 30.1	—	—	—
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 At Week 48	20 Probability of clinical worsening (%) Interval 5.6 to 34.0	17 Probability of clinical worsening (%) Interval 4.7 to 30.1	—	—	—
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 After Week 48	20 Probability of clinical worsening (%) Interval 5.6 to 34.0	17 Probability of clinical worsening (%) Interval 4.7 to 30.1	—	—	—

SECONDARY outcome

Timeframe: Baseline to Week 48+

Population: The Ambrisentan Only and Any Ambrisentan Groups were analyzed for Overall Survival

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.

Outcome measures

Measure	Ambrisentan Only n=33 Participants 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 n=37 Participants 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)
Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 At Week 4	0 Probability of death occurring (%) Interval 0.0 to 0.0	0 Probability of death occurring (%) Interval 0.0 to 0.0	—	—	—
Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 At Week 8	0 Probability of death occurring (%) Interval 0.0 to 0.0	0 Probability of death occurring (%) Interval 0.0 to 0.0	—	—	—
Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 At Week 12	0 Probability of death occurring (%) Interval 0.0 to 0.0	0 Probability of death occurring (%) Interval 0.0 to 0.0	—	—	—
Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 At Week 16	0 Probability of death occurring (%) Interval 0.0 to 0.0	0 Probability of death occurring (%) Interval 0.0 to 0.0	—	—	—
Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 At Week 20	0 Probability of death occurring (%) Interval 0.0 to 0.0	0 Probability of death occurring (%) Interval 0.0 to 0.0	—	—	—
Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 At Week 24	0 Probability of death occurring (%) Interval 0.0 to 0.0	0 Probability of death occurring (%) Interval 0.0 to 0.0	—	—	—
Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 At Week 28	0 Probability of death occurring (%) Interval 0.0 to 0.0	0 Probability of death occurring (%) Interval 0.0 to 0.0	—	—	—
Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 At Week 32	0 Probability of death occurring (%) Interval 0.0 to 0.0	0 Probability of death occurring (%) Interval 0.0 to 0.0	—	—	—
Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 At Week 36	0 Probability of death occurring (%) Interval 0.0 to 0.0	0 Probability of death occurring (%) Interval 0.0 to 0.0	—	—	—
Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 At Week 40	4 Probability of death occurring (%) Interval 0.0 to 10.8	3 Probability of death occurring (%) Interval 0.0 to 9.4	—	—	—
Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 At Week 44	4 Probability of death occurring (%) Interval 0.0 to 10.8	3 Probability of death occurring (%) Interval 0.0 to 9.4	—	—	—
Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 At Week 48	4 Probability of death occurring (%) Interval 0.0 to 10.8	3 Probability of death occurring (%) Interval 0.0 to 9.4	—	—	—
Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 After Week 48	4 Probability of death occurring (%) Interval 0.0 to 10.8	3 Probability of death occurring (%) Interval 0.0 to 9.4	—	—	—

Adverse Events

Ambrisentan Only

Serious events: 10 serious events

Other events: 32 other events

Deaths: 0 deaths

Any Ambrisentan

Serious events: 11 serious events

Other events: 36 other events

Deaths: 0 deaths

Any Placebo

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ambrisentan Only n=33 participants at risk 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)	Any Ambrisentan n=37 participants at risk Patients were assigned either ambrisentan or placebo at enrollment or randomization and received at least one dose of ambrisentan plus an approved PDE-5i	Any Placebo n=5 participants at risk Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i
Blood and lymphatic system disorders Anaemia	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Blood and lymphatic system disorders Pancytopenia	3.0% 1/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Cardiac disorders Atrial Flutter	3.0% 1/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Cardiac disorders Right ventricular failure	3.0% 1/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Cardiac disorders Myocardial infarction	0.00% 0/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Gastrointestinal disorders Gastrointestinal haemorrage	3.0% 1/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Gastrointestinal disorders Oesophageal splasm	3.0% 1/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Gastrointestinal disorders Abdominal pain	0.00% 0/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	20.0% 1/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
General disorders Chest discomfort	3.0% 1/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
General disorders Chest pain	3.0% 1/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Infections and infestations Cellulitis	3.0% 1/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Infections and infestations Diverticulitis	3.0% 1/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Infections and infestations Enterocolitis infectious	3.0% 1/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Infections and infestations Urinary tract infection	3.0% 1/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Metabolism and nutrition disorders Iron deficiency	3.0% 1/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Respiratory, thoracic and mediastinal disorders Hypoxia	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.

Other adverse events

Measure	Ambrisentan Only n=33 participants at risk 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)	Any Ambrisentan n=37 participants at risk Patients were assigned either ambrisentan or placebo at enrollment or randomization and received at least one dose of ambrisentan plus an approved PDE-5i	Any Placebo n=5 participants at risk Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i
Gastrointestinal disorders Abdominal discomfort	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Blood and lymphatic system disorders Anaemia	9.1% 3/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	8.1% 3/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Cardiac disorders Tachycardia	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	8.1% 3/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Ear and labyrinth disorders Deafness neurosensory	3.0% 1/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Gastrointestinal disorders Abdominal pain	9.1% 3/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	8.1% 3/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	20.0% 1/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Gastrointestinal disorders Gastrooesophageal reflux disease	9.1% 3/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	8.1% 3/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Gastrointestinal disorders Constipation	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	20.0% 1/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Gastrointestinal disorders Diarrhoea	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Gastrointestinal disorders Haemorrhoids	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Gastrointestinal disorders Nausea	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Gastrointestinal disorders Toothache	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
General disorders Oedema peripheral	21.2% 7/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	18.9% 7/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
General disorders Fatigue	15.2% 5/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	13.5% 5/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	20.0% 1/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
General disorders Chest pain	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Infections and infestations Upper respiratory tract infection	24.2% 8/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	21.6% 8/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Infections and infestations Urinary tract infection	15.2% 5/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	13.5% 5/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Infections and infestations Nasopharyngitis	9.1% 3/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	10.8% 4/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	20.0% 1/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Infections and infestations Lower respiratory tract infection	9.1% 3/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	8.1% 3/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Infections and infestations Sinusitis	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	8.1% 3/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Infections and infestations Cellulitis	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Infections and infestations Viral infection	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Infections and infestations Bronchitis	3.0% 1/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Investigations Brain natriuretic peptide increased	9.1% 3/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	8.1% 3/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Investigations Blood uric acid increased	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Investigations Protein total increased	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Investigations Urine leukocyte esterase positive	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Investigations Blood creatinine increased	3.0% 1/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	20.0% 1/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Metabolism and nutrition disorders Fluid overload	15.2% 5/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	18.9% 7/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	20.0% 1/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Metabolism and nutrition disorders Hypokalaemia	9.1% 3/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	8.1% 3/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	20.0% 1/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Metabolism and nutrition disorders Fluid retention	9.1% 3/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	8.1% 3/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Musculoskeletal and connective tissue disorders Arthralgia	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Musculoskeletal and connective tissue disorders Pain in extremity	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Nervous system disorders Headache	21.2% 7/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	18.9% 7/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	20.0% 1/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Nervous system disorders Dizziness	15.2% 5/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	13.5% 5/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	20.0% 1/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Nervous system disorders Carpal tunnel syndrome	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Psychiatric disorders Anxiety	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Psychiatric disorders Depression	3.0% 1/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	2.7% 1/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	20.0% 1/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Respiratory, thoracic and mediastinal disorders Nasal congestion	30.3% 10/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	27.0% 10/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Respiratory, thoracic and mediastinal disorders Dyspnoea	12.1% 4/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	10.8% 4/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Respiratory, thoracic and mediastinal disorders Epistaxis	12.1% 4/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	10.8% 4/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.
Respiratory, thoracic and mediastinal disorders Pulmonary arterial hypertension	6.1% 2/33 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	5.4% 2/37 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.	0.00% 0/5 • Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48. AEs/SAEs were analyzed for patients who: received ambrisentan but not placebo ("Ambrisentan Only"); received ambrisentan and did or did not receive placebo ("Any Ambrisentan"); received placebo and did or did not receive ambrisentan ("Any Placebo"). Safety analysis was not done for the "Ambrisentan/Placebo" or "Placebo Only" groups.

Additional Information

Ellen Shen, PhD, Senior Manager, Regulatory Affairs

Gilead Sciences

Phone: +1 (650) 522-5278

Email: Ellen.Shen@gilead.com

Results disclosure agreements

• Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
• Publication restrictions are in place

Restriction type: OTHER