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

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ClinicalTrials.gov Identifier: NCT00617305
Recruitment Status : Completed
First Posted : February 18, 2008
Results First Posted : July 30, 2012
Last Update Posted : July 30, 2012
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Pulmonary Arterial Hypertension
Interventions Drug: Ambrisentan
Drug: Placebo
Drug: Sildenafil
Drug: Tadalafil
Enrollment 38
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title Ambrisentan Only Placebo/Ambrisentan Placebo Only
Hide Arm/Group Description 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) 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 Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i
Period Title: Overall Study
Started 33 4 1
Completed 24-week Primary Analysis 31 4 0
Completed 25 4 0
Not Completed 8 0 1
Reason Not Completed
Adverse Event             4             0             0
Death             1             0             0
Physician Decision             1             0             0
Protocol Violation             1             0             1
Withdrawal by Subject             1             0             0
Arm/Group Title Ambrisentan Only Placebo/Ambrisentan Placebo Only Total
Hide Arm/Group Description 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) 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 Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i Total of all reporting groups
Overall Number of Baseline Participants 33 4 1 38
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 4 participants 1 participants 38 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
29
  87.9%
4
 100.0%
1
 100.0%
34
  89.5%
>=65 years
4
  12.1%
0
   0.0%
0
   0.0%
4
  10.5%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 33 participants 4 participants 1 participants 38 participants
48.2  (13.72) 43.5  (14.89) 49.0  (0) 47.8  (13.52)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 4 participants 1 participants 38 participants
Female
26
  78.8%
2
  50.0%
0
   0.0%
28
  73.7%
Male
7
  21.2%
2
  50.0%
1
 100.0%
10
  26.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 33 participants 4 participants 1 participants 38 participants
Hispanic or Latino
8
  24.2%
0
   0.0%
0
   0.0%
8
  21.1%
Not Hispanic or Latino
25
  75.8%
4
 100.0%
1
 100.0%
30
  78.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 33 participants 4 participants 1 participants 38 participants
Asian 2 0 0 2
Black or African American 2 0 0 2
Hispanic 1 0 0 1
More than one race 1 0 0 1
White 27 4 1 32
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 33 participants 4 participants 1 participants 38 participants
33 4 1 38
1.Primary Outcome
Title Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF)
Hide Description The primary objective of this study is to evaluate the change from baseline in PVR, and other hemodynamic parameters, following the addition of ambrisentan to background PDE-5i therapy in subjects with PAH who have demonstrated a sub-optimal response to PDE-5i monotherapy. A decrease in measurement value (dynes sec/cm^5) indicates improvement for this patient population.
Time Frame Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with measurements at Baseline and Week 24 were evaluated
Arm/Group Title Ambrisentan Only Placebo/Ambrisentan Placebo Only Any Ambrisentan Any Placebo
Hide Arm/Group Description:
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)
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)
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)
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)
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 Number of Participants Analyzed 31 4 0 35 4
Mean (Standard Deviation)
Unit of Measure: dynes sec/cm^5
Baseline 761.2  (306.57) 731.6  (278.02) 758.0  (300.12) 703.6  (248.73)
Week 24 518.8  (196.35) 439.8  (130.34) 509.8  (190.18) 439.8  (130.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -248.93
Confidence Interval (2-Sided) 95%
-337.7 to -160.2
Parameter Dispersion
Type: Standard Deviation
Value: 241.978
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -291.80
Confidence Interval (2-Sided) 95%
-619.4 to 35.78
Parameter Dispersion
Type: Standard Deviation
Value: 205.864
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -253.83
Confidence Interval (2-Sided) 95%
-334.8 to -172.8
Parameter Dispersion
Type: Standard Deviation
Value: 235.787
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -291.80
Confidence Interval (2-Sided) 95%
-619.4 to 35.78
Parameter Dispersion
Type: Standard Deviation
Value: 205.864
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF)
Hide Description This secondary hemodynamic outcome is supportive of the primary outcome. A decrease in measurement value (mmHg) indicates improvement for this patient population.
Time Frame Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with measurements at Baseline and Week 24 were evaluated
Arm/Group Title Ambrisentan Only Placebo/Ambrisentan Placebo Only Any Ambrisentan Any Placebo
Hide Arm/Group Description:
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)
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)
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)
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)
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 Number of Participants Analyzed 31 4 0 35 4
Mean (Standard Deviation)
Unit of Measure: mmHg
Baseline 49.9  (9.75) 54.5  (12.50) 50.4  (9.98) 52.8  (11.48)
Week 24 44.4  (10.95) 38.8  (9.60) 43.8  (10.83) 38.8  (9.60)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -5.38
Confidence Interval (2-Sided) 95%
-8.29 to -2.46
Parameter Dispersion
Type: Standard Deviation
Value: 7.954
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -15.75
Confidence Interval (2-Sided) 95%
-29.64 to -1.86
Parameter Dispersion
Type: Standard Deviation
Value: 8.732
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -6.56
Confidence Interval (2-Sided) 95%
-9.51 to -3.61
Parameter Dispersion
Type: Standard Deviation
Value: 8.589
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -15.75
Confidence Interval (2-Sided) 95%
-29.64 to -1.86
Parameter Dispersion
Type: Standard Deviation
Value: 8.732
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF)
Hide Description This secondary hemodynamic outcome is supportive of the primary outcome. A decrease in measurement value (mmHg) indicates improvement for this patient population.
Time Frame Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with measurements at Baseline and Week 24 were evaluated
Arm/Group Title Ambrisentan Only Placebo/Ambrisentan Placebo Only Any Ambrisentan Any Placebo
Hide Arm/Group Description:
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)
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)
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)
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)
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 Number of Participants Analyzed 31 4 0 35 4
Mean (Standard Deviation)
Unit of Measure: mmHg
Baseline 8.5  (4.82) 10.3  (2.63) 8.7  (4.64) 11.1  (2.97)
Week 24 8.4  (4.88) 6.3  (1.71) 8.1  (4.66) 6.3  (1.71)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.06
Confidence Interval (2-Sided) 95%
-1.69 to 1.56
Parameter Dispersion
Type: Standard Deviation
Value: 4.442
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.00
Confidence Interval (2-Sided) 95%
-10.50 to 2.50
Parameter Dispersion
Type: Standard Deviation
Value: 4.082
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.51
Confidence Interval (2-Sided) 95%
-2.07 to 1.04
Parameter Dispersion
Type: Standard Deviation
Value: 4.527
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.00
Confidence Interval (2-Sided) 95%
-10.50 to 2.50
Parameter Dispersion
Type: Standard Deviation
Value: 4.082
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in Cardiac Output (LOCF)
Hide Description This secondary hemodynamic outcome is supportive of the primary outcome. An increase in measurement value (L/min) indicates improvement for this patient population.
Time Frame Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with measurements at Baseline and Week 24 were evaluated
Arm/Group Title Ambrisentan Only Placebo/Ambrisentan Placebo Only Any Ambrisentan Any Placebo
Hide Arm/Group Description:
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)
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)
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)
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)
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 Number of Participants Analyzed 28 4 0 32 4
Mean (Standard Deviation)
Unit of Measure: L/min
Baseline 4.4  (1.22) 4.8  (0.81) 4.4  (1.17) 4.8  (0.71)
Week 24 5.2  (1.27) 5.2  (1.22) 5.2  (1.24) 5.2  (1.22)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.43 to 1.25
Parameter Dispersion
Type: Standard Deviation
Value: 1.053
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
-0.77 to 1.42
Parameter Dispersion
Type: Standard Deviation
Value: 0.685
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.41 to 1.15
Parameter Dispersion
Type: Standard Deviation
Value: 1.021
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
-0.77 to 1.42
Parameter Dispersion
Type: Standard Deviation
Value: 0.685
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Hide Description The primary analysis of this secondary outcome measure is mean change from Baseline to Week 24. The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated. An increase in measurement value (meters walked) indicates improvement for this patient population.
Time Frame Baseline to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled Population
Arm/Group Title Ambrisentan Only Placebo/Ambrisentan Placebo Only Any Ambrisentan Any Placebo
Hide Arm/Group Description:
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)
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)
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)
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)
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 Number of Participants Analyzed 33 4 1 37 5
Mean (Standard Deviation)
Unit of Measure: meters walked
Baseline 361.9  (98.74) 433.3  (80.77) 335.0  (0.0) 369.6  (98.56) 413.6  (82.61)
Week 4 376.5  (106.08) 441.0  (83.88) 442.0  (0.0) 383.7  (104.85) 441.2  (72.65)
Week 12 377.9  (109.61) 435.8  (134.61) 422.0  (0.0) 384.3  (111.96) 433.0  (116.74)
Week 24 382.4  (104.96) 423.8  (110.05) 422.0  (0.0) 387.0  (104.73) 423.4  (95.31)
Week 36 366.5  (127.62) 399.3  (152.93) 402.0  (0.0) 370.2  (128.61) 399.8  (132.45)
Week 48 378.9  (124.18) 383.5  (192.47) 402.0  (0.0) 379.4  (129.75) 387.2  (166.89)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 12.2
Confidence Interval (2-Sided) 95%
-3.9 to 28.4
Parameter Dispersion
Type: Standard Deviation
Value: 44.84
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 7.8
Confidence Interval (2-Sided) 95%
-26.0 to 41.5
Parameter Dispersion
Type: Standard Deviation
Value: 21.19
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Only
Comments Mean change from Baseline to Week 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 107.0
Parameter Dispersion
Type: Standard Deviation
Value: 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 11.7
Confidence Interval (2-Sided) 95%
-2.7 to 26.2
Parameter Dispersion
Type: Standard Deviation
Value: 42.68
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 27.6
Confidence Interval (2-Sided) 95%
-32.0 to 87.2
Parameter Dispersion
Type: Standard Deviation
Value: 48.03
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 13.6
Confidence Interval (2-Sided) 95%
-1.4 to 28.5
Parameter Dispersion
Type: Standard Deviation
Value: 41.46
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.5
Confidence Interval (2-Sided) 95%
-91.5 to 96.5
Parameter Dispersion
Type: Standard Deviation
Value: 59.09
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo Only
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 87.0
Parameter Dispersion
Type: Standard Deviation
Value: 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 12.4
Confidence Interval (2-Sided) 95%
-2.1 to 26.9
Parameter Dispersion
Type: Standard Deviation
Value: 42.83
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 19.4
Confidence Interval (2-Sided) 95%
-59.6 to 98.4
Parameter Dispersion
Type: Standard Deviation
Value: 63.61
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 18.1
Confidence Interval (2-Sided) 95%
0.5 to 35.6
Parameter Dispersion
Type: Standard Deviation
Value: 48.67
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -9.5
Confidence Interval (2-Sided) 95%
-56.5 to 37.5
Parameter Dispersion
Type: Standard Deviation
Value: 29.56
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo Only
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 87.0
Parameter Dispersion
Type: Standard Deviation
Value: 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 15.0
Confidence Interval (2-Sided) 95%
-1.0 to 31.1
Parameter Dispersion
Type: Standard Deviation
Value: 47.44
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 9.8
Confidence Interval (2-Sided) 95%
-52.5 to 72.1
Parameter Dispersion
Type: Standard Deviation
Value: 50.18
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.2
Confidence Interval (2-Sided) 95%
-25.6 to 30.1
Parameter Dispersion
Type: Standard Deviation
Value: 77.24
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -34.0
Confidence Interval (2-Sided) 95%
-182.2 to 114.2
Parameter Dispersion
Type: Standard Deviation
Value: 93.16
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo Only
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 67.0
Parameter Dispersion
Type: Standard Deviation
Value: 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.8
Confidence Interval (2-Sided) 95%
-28.4 to 24.8
Parameter Dispersion
Type: Standard Deviation
Value: 78.50
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -13.8
Confidence Interval (2-Sided) 95%
-128.6 to 101.0
Parameter Dispersion
Type: Standard Deviation
Value: 92.46
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 14.6
Confidence Interval (2-Sided) 95%
-15.0 to 44.2
Parameter Dispersion
Type: Standard Deviation
Value: 82.07
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -49.8
Confidence Interval (2-Sided) 95%
-251.4 to 151.9
Parameter Dispersion
Type: Standard Deviation
Value: 126.75
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Placebo Only
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 67.0
Parameter Dispersion
Type: Standard Deviation
Value: 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 7.4
Confidence Interval (2-Sided) 95%
-22.4 to 37.3
Parameter Dispersion
Type: Standard Deviation
Value: 88.11
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -26.4
Confidence Interval (2-Sided) 95%
-177.3 to 124.5
Parameter Dispersion
Type: Standard Deviation
Value: 121.55
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Hide Description The primary analysis of this secondary outcome measure is mean change from Baseline to Week 24. The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated. The dyspnea index measures the degree of breathlessness after completion of the 6MWT using a scale of 0 to 10, with 0 indicating no breathlessness and 10 indicating maximum breathlessness.
Time Frame Baseline to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled Population
Arm/Group Title Ambrisentan Only Placebo/Ambrisentan Placebo Only Any Ambrisentan Any Placebo
Hide Arm/Group Description:
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)
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)
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)
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)
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 Number of Participants Analyzed 33 4 1 37 5
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 3.7  (2.07) 2.5  (1.29) 3.0  (0.0) 3.6  (2.03) 2.6  (1.14)
Week 4 3.2  (1.68) 3.3  (2.22) 2.0  (0.0) 3.2  (1.71) 3.0  (2.00)
Week 12 3.2  (1.94) 4.0  (2.83) 3.0  (0.0) 3.3  (2.02) 3.8  (2.49)
Week 24 2.9  (1.96) 1.9  (1.31) 3.0  (0.0) 2.8  (1.91) 2.1  (1.24)
Week 36 3.2  (2.29) 3.5  (2.65) 3.0  (0.0) 3.2  (2.29) 3.4  (2.30)
Week 48 3.1  (2.32) 3.5  (4.04) 3.0  (0.0) 3.1  (2.49) 3.4  (3.51)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.1 to 0.0
Parameter Dispersion
Type: Standard Deviation
Value: 1.50
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-1.6 to 3.1
Parameter Dispersion
Type: Standard Deviation
Value: 1.50
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Only
Comments Mean change from Baseline to Week 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.0
Parameter Dispersion
Type: Standard Deviation
Value: 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-0.9 to 0.1
Parameter Dispersion
Type: Standard Deviation
Value: 1.54
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-1.5 to 2.3
Parameter Dispersion
Type: Standard Deviation
Value: 1.52
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.1 to 0.0
Parameter Dispersion
Type: Standard Deviation
Value: 1.45
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
-2.3 to 5.3
Parameter Dispersion
Type: Standard Deviation
Value: 2.38
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo Only
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Parameter Dispersion
Type: Standard Deviation
Value: 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-0.9 to 0.2
Parameter Dispersion
Type: Standard Deviation
Value: 1.67
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-1.5 to 3.9
Parameter Dispersion
Type: Standard Deviation
Value: 2.17
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-1.5 to -0.2
Parameter Dispersion
Type: Standard Deviation
Value: 1.81
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.8 to 0.6
Parameter Dispersion
Type: Standard Deviation
Value: 0.75
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo Only
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Parameter Dispersion
Type: Standard Deviation
Value: 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-1.4 to -0.3
Parameter Dispersion
Type: Standard Deviation
Value: 1.72
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.4 to 0.4
Parameter Dispersion
Type: Standard Deviation
Value: 0.71
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.2 to 0.1
Parameter Dispersion
Type: Standard Deviation
Value: 1.79
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
-2.2 to 4.2
Parameter Dispersion
Type: Standard Deviation
Value: 2.00
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo Only
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Parameter Dispersion
Type: Standard Deviation
Value: 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.0 to 0.2
Parameter Dispersion
Type: Standard Deviation
Value: 1.85
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-1.4 to 3.0
Parameter Dispersion
Type: Standard Deviation
Value: 1.79
Estimation Comments [Not Specified]
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.4 to 0.1
Parameter Dispersion
Type: Standard Deviation
Value: 2.12
Estimation Comments [Not Specified]
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.0
Confidence Interval (2-Sided) 95%
-4.5 to 6.5
Parameter Dispersion
Type: Standard Deviation
Value: 3.46
Estimation Comments [Not Specified]
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Placebo Only
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.0
Parameter Dispersion
Type: Standard Deviation
Value: 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-1.3 to 0.3
Parameter Dispersion
Type: Standard Deviation
Value: 2.30
Estimation Comments [Not Specified]
Show Statistical Analysis 25 Hide Statistical Analysis 25
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-3.0 to 4.6
Parameter Dispersion
Type: Standard Deviation
Value: 3.03
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in the Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) Quality of Life (QOL) Survey Overall Score Measured at Weeks 12, 24, 36 and 48 (LOCF)
Hide Description The primary analysis of this secondary outcome measure is mean change from Baseline to Week 24. The changes from Baseline to Weeks 12, 36, and 48 were also evaluated. Lower scores and decreases from baseline represent improved functioning and QOL. The CAMPHOR survey was not assessed at Week 4. The total CAMPHOR score scale ranges from 0 (good) to 25 (poor). A reduction in score over time represents improvement in this patient population.
Time Frame Baseline to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled Population
Arm/Group Title Ambrisentan Only Placebo/Ambrisentan Placebo Only Any Ambrisentan Any Placebo
Hide Arm/Group Description:
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)
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)
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)
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)
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 Number of Participants Analyzed 33 4 1 37 5
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline 8.2  (6.14) 4.3  (5.44) 4.0  (0.0) 7.7  (6.12) 4.2  (4.71)
Week 12 6.8  (5.59) 5.5  (3.11) 2.0  (0.0) 6.7  (5.32) 4.8  (3.11)
Week 24 7.2  (5.82) 3.0  (2.94) 2.0  (0.0) 6.7  (5.69) 2.8  (2.59)
Week 36 7.7  (6.10) 3.5  (3.70) 3.0  (0.0) 7.2  (5.98) 3.4  (3.21)
Week48 7.6  (6.87) 3.8  (3.50) 3.0  (0.0) 7.1  (6.63) 3.6  (3.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.1
Confidence Interval (2-Sided) 95%
-2.7 to 0.4
Parameter Dispersion
Type: Standard Deviation
Value: 3.98
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-6.5 to 9.0
Parameter Dispersion
Type: Standard Deviation
Value: 4.86
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo Only
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.0
Parameter Dispersion
Type: Standard Deviation
Value: 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.3 to 0.6
Parameter Dispersion
Type: Standard Deviation
Value: 4.09
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-4.9 to 6.1
Parameter Dispersion
Type: Standard Deviation
Value: 4.45
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.7 to 1.1
Parameter Dispersion
Type: Standard Deviation
Value: 5.00
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.3
Confidence Interval (2-Sided) 95%
-7.7 to 5.2
Parameter Dispersion
Type: Standard Deviation
Value: 4.03
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo Only
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.0
Parameter Dispersion
Type: Standard Deviation
Value: 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.9
Confidence Interval (2-Sided) 95%
-2.6 to 0.9
Parameter Dispersion
Type: Standard Deviation
Value: 4.84
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.4
Confidence Interval (2-Sided) 95%
-5.8 to 3.0
Parameter Dispersion
Type: Standard Deviation
Value: 3.51
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-2.3 to 1.7
Parameter Dispersion
Type: Standard Deviation
Value: 5.20
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-8.1 to 6.6
Parameter Dispersion
Type: Standard Deviation
Value: 4.65
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Placebo Only
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.0
Parameter Dispersion
Type: Standard Deviation
Value: 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.3
Confidence Interval (2-Sided) 95%
-2.2 to 1.5
Parameter Dispersion
Type: Standard Deviation
Value: 5.07
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-5.8 to 4.2
Parameter Dispersion
Type: Standard Deviation
Value: 4.02
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-2.8 to 2.1
Parameter Dispersion
Type: Standard Deviation
Value: 6.33
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.5
Confidence Interval (2-Sided) 95%
-11.4 to 10.4
Parameter Dispersion
Type: Standard Deviation
Value: 6.86
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo Only
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.0
Parameter Dispersion
Type: Standard Deviation
Value: 0.0
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-2.7 to 1.9
Parameter Dispersion
Type: Standard Deviation
Value: 6.28
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-8.0 to 6.8
Parameter Dispersion
Type: Standard Deviation
Value: 5.94
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48.
Hide Description The primary analysis of this secondary outcome measure is change from Baseline to Week 24. The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated. WHO categories are 1 to 4 with the worst category being 4. Improvement is represented by a change in category to a lower number (for example, change from category 3 to 2), and deterioration is represented by a change in category to a higher number (for example, change from category 2 to 4). No change is represented by no change in category (for example, category 2 which remains 2).
Time Frame Baseline to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
All enrolled Population
Arm/Group Title Ambrisentan Only Placebo/Ambrisentan Placebo Only Any Ambrisentan Any Placebo
Hide Arm/Group Description:
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)
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)
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)
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)
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 Number of Participants Analyzed 33 4 1 37 5
Measure Type: Number
Unit of Measure: participants
Week 4 - Improvement 3 0 1 3 1
Week 4 - No Change 29 4 0 33 4
Week 4 - Deterioration 0 0 0 0 0
Week 4 - Missing Data 1 0 0 1 0
Week 12 - Improvement 8 1 1 9 2
Week 12 - No Change 24 3 0 27 3
Week 12 - Deterioration 0 0 0 0 0
Week 12 - Missing Data 1 0 0 1 0
Week 24 - Improvement 12 2 1 14 3
Week 24 - No Change 19 2 0 21 2
Week 24 - Deterioration 1 0 0 1 0
Week 24 - Missing Data 1 0 0 1 0
Week 36 - Improvement 17 2 1 19 3
Week 36 - No Change 14 2 0 16 2
Week 36 - Deterioration 1 0 0 1 0
Week 36 - Missing Data 1 0 0 1 0
Week 48 - Improvement 14 1 1 15 2
Week 48 - No Change 17 3 0 20 3
Week 48 - Deterioration 1 0 0 1 0
Week 48 - Missing Data 1 0 0 1 0
9.Secondary Outcome
Title Change From Baseline in Log-transformed N-terminal Pro-B-type Natriuretic Peptide (NT-proBNP) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
Hide Description The primary analysis of this secondary outcome measure is mean percent change from Baseline to Week 24. The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated. A decrease in log-transformed measurement value (pg/mL) indicates improvement for this patient population.
Time Frame Baseline to Week 48
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Ambrisentan Only Placebo/Ambrisentan Placebo Only Any Ambrisentan Any Placebo
Hide Arm/Group Description:
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)
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)
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)
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)
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 Number of Participants Analyzed 33 4 1 37 4
Mean (Standard Deviation)
Unit of Measure: pg/mL (log-transformed)
Baseline 6.1  (1.10) 6.7  (1.02) 0.0  (0.0) 6.2  (1.10) 6.7  (1.02)
Week 4 5.7  (1.02) 6.2  (1.80) 7.5  (0.0) 5.7  (1.05) 6.7  (1.46)
Week 12 5.7  (1.01) 6.3  (0.45) 7.6  (0.0) 5.8  (0.99) 6.8  (0.80)
Week 24 5.7  (1.03) 6.0  (0.98) 7.6  (0.0) 5.7  (1.02) 6.4  (1.12)
Week 36 5.7  (1.19) 5.9  (0.64) 8.0  (0.0) 5.7  (1.14) 6.3  (1.08)
Week 48 5.6  (1.16) 6.4  (0.82) 8.0  (0.0) 5.7  (1.14) 6.7  (1.01)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Parameter Dispersion
Type: Standard Deviation
Value: 0.50
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Parameter Dispersion
Type: Standard Deviation
Value: 0.28
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Parameter Dispersion
Type: Standard Deviation
Value: 0.49
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 4 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.2
Parameter Dispersion
Type: Standard Deviation
Value: 0.28
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.3
Parameter Dispersion
Type: Standard Deviation
Value: 0.63
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Parameter Dispersion
Type: Standard Deviation
Value: 1.07
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.3
Parameter Dispersion
Type: Standard Deviation
Value: 0.64
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 12 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.1
Parameter Dispersion
Type: Standard Deviation
Value: 1.07
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Parameter Dispersion
Type: Standard Deviation
Value: 0.83
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.7
Parameter Dispersion
Type: Standard Deviation
Value: 0.34
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Parameter Dispersion
Type: Standard Deviation
Value: 0.81
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 24 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.7
Parameter Dispersion
Type: Standard Deviation
Value: 0.34
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Parameter Dispersion
Type: Standard Deviation
Value: 0.92
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.8
Parameter Dispersion
Type: Standard Deviation
Value: 0.90
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Parameter Dispersion
Type: Standard Deviation
Value: 0.91
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 36 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.8
Parameter Dispersion
Type: Standard Deviation
Value: 0.90
Estimation Comments [Not Specified]
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Ambrisentan Only
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Parameter Dispersion
Type: Standard Deviation
Value: 0.91
Estimation Comments [Not Specified]
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Placebo/Ambrisentan
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.3
Parameter Dispersion
Type: Standard Deviation
Value: 0.77
Estimation Comments [Not Specified]
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Any Ambrisentan
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.4
Parameter Dispersion
Type: Standard Deviation
Value: 0.88
Estimation Comments [Not Specified]
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Any Placebo
Comments Mean change from Baseline to Week 48 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.3
Parameter Dispersion
Type: Standard Deviation
Value: 0.77
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Time to Clinical Worsening of PAH, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48
Hide Description The time to clinical worsening was defined as the time from enrollment to the first occurrence of death, lung transplantation, hospitalization for PAH, atrial septostomy, or initiation of chronic parenteral prostanoid therapy. Results are presented as the Kaplan-Meier estimate (% probability) of having clinical worsening after a given time.
Time Frame Baseline to Week 48+
Hide Outcome Measure Data
Hide Analysis Population Description
The Ambrisentan Only and Any Ambrisentan Groups were analyzed for Time to Clinical Worsening
Arm/Group Title Ambrisentan Only Any Ambrisentan
Hide Arm/Group Description:
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)
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)
Overall Number of Participants Analyzed 33 37
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Probability of clinical worsening (%)
At Week 4
0
(0.0 to 0.0)
0
(0.0 to 0.0)
At Week 8
0
(0.0 to 0.0)
0
(0.0 to 0.0)
At Week 12
0
(0.0 to 0.0)
0
(0.0 to 0.0)
At Week 16
0
(0.0 to 0.0)
0
(0.0 to 0.0)
At Week 20
3
(0.0 to 9.1)
3
(0.0 to 8.2)
At Week 24
3
(0.0 to 9.1)
3
(0.0 to 8.2)
At Week 28
6
(0.0 to 14.7)
6
(0.0 to 13.1)
At Week 32
16
(3.1 to 29.1)
14
(2.7 to 25.9)
At Week 36
16
(3.1 to 29.1)
14
(2.7 to 25.9)
At Week 40
20
(5.6 to 34.0)
17
(4.7 to 30.1)
At Week 44
20
(5.6 to 34.0)
17
(4.7 to 30.1)
At Week 48
20
(5.6 to 34.0)
17
(4.7 to 30.1)
After Week 48
20
(5.6 to 34.0)
17
(4.7 to 30.1)
11.Secondary Outcome
Title Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48
Hide Description Overall survival was defined as the time from initiation of active treatment to death. Results are presented as the Kaplan-Meier estimate (% probability) of death after a given time.
Time Frame Baseline to Week 48+
Hide Outcome Measure Data
Hide Analysis Population Description
The Ambrisentan Only and Any Ambrisentan Groups were analyzed for Overall Survival
Arm/Group Title Ambrisentan Only Any Ambrisentan
Hide Arm/Group Description:
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)
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)
Overall Number of Participants Analyzed 33 37
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Probability of death occurring (%)
At Week 4
0
(0.0 to 0.0)
0
(0.0 to 0.0)
At Week 8
0
(0.0 to 0.0)
0
(0.0 to 0.0)
At Week 12
0
(0.0 to 0.0)
0
(0.0 to 0.0)
At Week 16
0
(0.0 to 0.0)
0
(0.0 to 0.0)
At Week 20
0
(0.0 to 0.0)
0
(0.0 to 0.0)
At Week 24
0
(0.0 to 0.0)
0
(0.0 to 0.0)
At Week 28
0
(0.0 to 0.0)
0
(0.0 to 0.0)
At Week 32
0
(0.0 to 0.0)
0
(0.0 to 0.0)
At Week 36
0
(0.0 to 0.0)
0
(0.0 to 0.0)
At Week 40
4
(0.0 to 10.8)
3
(0.0 to 9.4)
At Week 44
4
(0.0 to 10.8)
3
(0.0 to 9.4)
At Week 48
4
(0.0 to 10.8)
3
(0.0 to 9.4)
After Week 48
4
(0.0 to 10.8)
3
(0.0 to 9.4)
Time Frame Adverse events (AEs) and serious adverse events (SAEs) were reported through Week 48.
Adverse Event Reporting Description 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.
 
Arm/Group Title Ambrisentan Only Any Ambrisentan Any Placebo
Hide Arm/Group Description 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) Patients were assigned either ambrisentan or placebo at enrollment or randomization and received at least one dose of ambrisentan plus an approved PDE-5i Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i
All-Cause Mortality
Ambrisentan Only Any Ambrisentan Any Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Ambrisentan Only Any Ambrisentan Any Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   10/33 (30.30%)   11/37 (29.73%)   1/5 (20.00%) 
Blood and lymphatic system disorders       
Anaemia * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Pancytopenia * 1  1/33 (3.03%)  1/37 (2.70%)  0/5 (0.00%) 
Cardiac disorders       
Atrial Flutter * 1  1/33 (3.03%)  1/37 (2.70%)  0/5 (0.00%) 
Right ventricular failure * 1  1/33 (3.03%)  1/37 (2.70%)  0/5 (0.00%) 
Myocardial infarction * 1  0/33 (0.00%)  1/37 (2.70%)  0/5 (0.00%) 
Gastrointestinal disorders       
Gastrointestinal haemorrage * 1  1/33 (3.03%)  1/37 (2.70%)  0/5 (0.00%) 
Oesophageal splasm * 1  1/33 (3.03%)  1/37 (2.70%)  0/5 (0.00%) 
Abdominal pain * 1  0/33 (0.00%)  0/37 (0.00%)  1/5 (20.00%) 
General disorders       
Chest discomfort * 1  1/33 (3.03%)  1/37 (2.70%)  0/5 (0.00%) 
Chest pain * 1  1/33 (3.03%)  1/37 (2.70%)  0/5 (0.00%) 
Infections and infestations       
Cellulitis * 1  1/33 (3.03%)  1/37 (2.70%)  0/5 (0.00%) 
Diverticulitis * 1  1/33 (3.03%)  1/37 (2.70%)  0/5 (0.00%) 
Enterocolitis infectious * 1  1/33 (3.03%)  1/37 (2.70%)  0/5 (0.00%) 
Urinary tract infection * 1  1/33 (3.03%)  1/37 (2.70%)  0/5 (0.00%) 
Metabolism and nutrition disorders       
Iron deficiency * 1  1/33 (3.03%)  1/37 (2.70%)  0/5 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Dyspnoea * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Hypoxia * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Pulmonary arterial hypertension * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Pneumonitis * 1  0/33 (0.00%)  1/37 (2.70%)  0/5 (0.00%) 
Respiratory failure * 1  0/33 (0.00%)  1/37 (2.70%)  0/5 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ambrisentan Only Any Ambrisentan Any Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   32/33 (96.97%)   36/37 (97.30%)   4/5 (80.00%) 
Blood and lymphatic system disorders       
Anaemia * 1  3/33 (9.09%)  3/37 (8.11%)  0/5 (0.00%) 
Cardiac disorders       
Tachycardia * 1  2/33 (6.06%)  3/37 (8.11%)  0/5 (0.00%) 
Ear and labyrinth disorders       
Deafness neurosensory * 1  1/33 (3.03%)  2/37 (5.41%)  0/5 (0.00%) 
Gastrointestinal disorders       
Abdominal pain * 1  3/33 (9.09%)  3/37 (8.11%)  1/5 (20.00%) 
Gastrooesophageal reflux disease * 1  3/33 (9.09%)  3/37 (8.11%)  0/5 (0.00%) 
Constipation * 1  2/33 (6.06%)  2/37 (5.41%)  1/5 (20.00%) 
Abdominal discomfort * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Diarrhoea * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Haemorrhoids * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Nausea * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Toothache * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
General disorders       
Oedema peripheral * 1  7/33 (21.21%)  7/37 (18.92%)  0/5 (0.00%) 
Fatigue * 1  5/33 (15.15%)  5/37 (13.51%)  1/5 (20.00%) 
Chest pain * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Infections and infestations       
Upper respiratory tract infection * 1  8/33 (24.24%)  8/37 (21.62%)  0/5 (0.00%) 
Urinary tract infection * 1  5/33 (15.15%)  5/37 (13.51%)  0/5 (0.00%) 
Nasopharyngitis * 1  3/33 (9.09%)  4/37 (10.81%)  1/5 (20.00%) 
Lower respiratory tract infection * 1  3/33 (9.09%)  3/37 (8.11%)  0/5 (0.00%) 
Sinusitis * 1  2/33 (6.06%)  3/37 (8.11%)  0/5 (0.00%) 
Cellulitis * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Viral infection * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Bronchitis * 1  1/33 (3.03%)  2/37 (5.41%)  0/5 (0.00%) 
Investigations       
Brain natriuretic peptide increased * 1  3/33 (9.09%)  3/37 (8.11%)  0/5 (0.00%) 
Blood uric acid increased * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Protein total increased * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Urine leukocyte esterase positive * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Blood creatinine increased * 1  1/33 (3.03%)  1/37 (2.70%)  1/5 (20.00%) 
Metabolism and nutrition disorders       
Fluid overload * 1  5/33 (15.15%)  7/37 (18.92%)  1/5 (20.00%) 
Hypokalaemia * 1  3/33 (9.09%)  3/37 (8.11%)  1/5 (20.00%) 
Fluid retention * 1  3/33 (9.09%)  3/37 (8.11%)  0/5 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Musculoskeletal pain * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Pain in extremity * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Nervous system disorders       
Headache * 1  7/33 (21.21%)  7/37 (18.92%)  1/5 (20.00%) 
Dizziness * 1  5/33 (15.15%)  5/37 (13.51%)  1/5 (20.00%) 
Carpal tunnel syndrome * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Psychiatric disorders       
Anxiety * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Depression * 1  1/33 (3.03%)  1/37 (2.70%)  1/5 (20.00%) 
Respiratory, thoracic and mediastinal disorders       
Nasal congestion * 1  10/33 (30.30%)  10/37 (27.03%)  0/5 (0.00%) 
Dyspnoea * 1  4/33 (12.12%)  4/37 (10.81%)  0/5 (0.00%) 
Epistaxis * 1  4/33 (12.12%)  4/37 (10.81%)  0/5 (0.00%) 
Oropharyngeal pain * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
Pulmonary arterial hypertension * 1  2/33 (6.06%)  2/37 (5.41%)  0/5 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 14.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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
Results Point of Contact
Name/Title: Ellen Shen, PhD, Senior Manager, Regulatory Affairs
Organization: Gilead Sciences
Phone: +1 (650) 522-5278
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00617305     History of Changes
Other Study ID Numbers: GS-US-300-0117
First Submitted: February 6, 2008
First Posted: February 18, 2008
Results First Submitted: May 11, 2012
Results First Posted: July 30, 2012
Last Update Posted: July 30, 2012