Pulmonary Arterial Hypertension
Conditions
Keywords
ambrisentan, PAH, combination therapy, phosphodiesterase type-5 inhibitor (PDE-5i), cardiovascular, endothelin receptor antagonist, ERA
Brief summary
To evaluate the change from baseline in pulmonary vascular resistance (PVR), and other hemodynamic parameters, following the addition of ambrisentan to background phosphodiesterase type-5 inhibitor (PDE-5i) therapy in subjects with pulmonary arterial hypertension (PAH) who have demonstrated a sub-optimal response to PDE-5i monotherapy. The study was originally designed as a 2-arm, double-blind, randomized study in which patients received ambrisentan or placebo for 24 weeks, and then received ambrisentan blinded to dose for 24 weeks. With Protocol Amendment 2 (12 June, 2009), the study was switched to single-arm, open-label treatment, and all patients remaining in the placebo arm were switched to open-label ambrisentan treatment. Patients who enrolled after Amendment 2 all received open-label ambrisentan.
Detailed description
The primary objective of this study is to evaluate the change from baseline in pulmonary vascular resistance (PVR), and other hemodynamic parameters, following the addition of ambrisentan to background phosphodiesterase type-5 inhibitor (PDE-5i) therapy in subjects with pulmonary arterial hypertension (PAH) who have demonstrated a sub-optimal response to PDE-5i monotherapy. The secondary objectives of this study are to evaluate the change from baseline in other clinical measures of PAH 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. The safety and tolerability of ambrisentan/PDE-5i combination therapy will be evaluated throughout the study. In addition, long-term efficacy will be examined.
Interventions
DRUGAmbrisentan
Ambrisentan was administered orally once daily; dose level was 5 mg for the first 4 weeks, followed by 10 mg for the remainder of the study; ambrisentan was supplied as 5-mg and 10-mg tablets.
DRUGPlacebo
Placebo to match ambrisentan was administered orally once daily.
DRUGSildenafil
Sildenafil was administered at the dose previously established for each subject (20-100 mg) orally three times daily. Sildenafil was supplied as 20-mg tablets, or formulated as sildenafil citrate in 25-, 50-, or 100-mg tablets.
DRUGTadalafil
Tadalafil was administered at the dose previously established for each subject (not to exceed 40 mg per day) orally once daily. Tadalafil was supplied as 20-mg tablets.
Sponsors
Gilead Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Selected Inclusion Criteria * Must be between 16 and 75 years of age; * Must weigh at least 40 kg; * Have a current diagnosis of idiopathic PAH, familial PAH, or PAH that is primarily due to connective tissue disease, congenital heart defects, drug or toxin use, or human immunodeficiency virus (HIV); * Have WHO functional class III symptoms; * Be receiving sildenafil or tadalafil monotherapy for the treatment of PAH for at least the past 12 weeks and at a stable dose for at least 8 consecutive weeks; * Meet all of the following hemodynamic criteria by means of a right heart catheterization: mPAP of at least 25 mmHg; PVR of at least 400 dyne\*sec/cm5; pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) of not more than 15 mmHg; * Meet all of the following pulmonary function test criteria no more than 12 weeks before the screening visit: total lung capacity at least 60% of predicted normal and forced expiratory volume in 1 second of at least 65% of predicted normal; * Able to walk at least 150 meters during the screening 6-minute walk test (6MWT); * If receiving calcium channel blockers or 5-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (i.e., statins) must be on stable therapy for at least 4 weeks; * If diagnosed with HIV, must have stable disease status. Selected
Exclusion criteria
* Have a current pulmonary hypertension diagnosis other than idiopathic PAH, familial PAH, or PAH that is primarily due to connective tissue disease, congenital heart defects, drug or toxin use, or HIV; * Have left ventricular ejection fraction (LVEF) ≤40% or clinically significant ischemic, valvular, or constrictive heart disease; * Have received chronic prostanoid or endothelin receptor antagonist (ERA) therapy (eg, bosentan, sitaxsentan) within the past 12 weeks; * Have discontinued ERA treatment for any adverse reaction other than those associated with liver function test abnormalities; * Have received IV inotropes within 2 weeks; * Have a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) value that is greater than 2.0x the upper limit of normal.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF) | Baseline to Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF) | Baseline to Week 24 | This secondary hemodynamic outcome is supportive of the primary outcome. A decrease in measurement value (mmHg) indicates improvement for this patient population. |
| Change From Baseline in Cardiac Output (LOCF) | Baseline to Week 24 | This secondary hemodynamic outcome is supportive of the primary outcome. An increase in measurement value (L/min) indicates improvement for this patient population. |
| Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Baseline to Week 48 | 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. |
| Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Baseline to Week 48 | 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. |
| Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF) | Baseline to Week 24 | This secondary hemodynamic outcome is supportive of the primary outcome. A decrease in measurement value (mmHg) indicates improvement for this patient population. |
| Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Baseline to Week 48 | 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). |
| 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 to Week 48 | 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 to Clinical Worsening of PAH, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 | Baseline to Week 48+ | 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. |
| Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 | Baseline to Week 48+ | 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. |
| 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 to Week 48 | 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. |
Countries
United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Ambrisentan Only Patients were assigned ambrisentan at open-label enrollment or randomization, and received at least one dose of ambrisentan plus an approved phosphodiesterase type-5 (PDE-5) inhibitor (PDE-5i) | 33 |
| Placebo/Ambrisentan Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i; patients also received at least one dose of open-label ambrisentan plus an approved PDE-5i | 4 |
| Placebo Only Patients were assigned placebo at randomization and received at least one dose of placebo plus an approved PDE-5i | 1 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| 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
| Characteristic | Ambrisentan Only | Placebo/Ambrisentan | Placebo Only | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 0 Participants | 0 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 4 Participants | 1 Participants | 34 Participants |
| Age Continuous | 48.2 years STANDARD_DEVIATION 13.72 | 43.5 years STANDARD_DEVIATION 14.89 | 49.0 years STANDARD_DEVIATION 0 | 47.8 years STANDARD_DEVIATION 13.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants | 0 Participants | 0 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 25 Participants | 4 Participants | 1 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 participants | 0 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Black or African American | 2 participants | 0 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Hispanic | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized More than one race | 1 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 27 participants | 4 participants | 1 participants | 32 participants |
| Region of Enrollment United States | 33 participants | 4 participants | 1 participants | 38 participants |
| Sex: Female, Male Female | 26 Participants | 2 Participants | 0 Participants | 28 Participants |
| Sex: Female, Male Male | 7 Participants | 2 Participants | 1 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 32 / 33 | 36 / 37 | 4 / 5 |
| serious Total, serious adverse events | 10 / 33 | 11 / 37 | 1 / 5 |
Outcome results
Primary
Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF)
The primary objective of this study is to evaluate the change from baseline in PVR, and other hemodynamic parameters, following the addition of ambrisentan to background PDE-5i therapy in subjects with PAH who have demonstrated a sub-optimal response to PDE-5i monotherapy. A decrease in measurement value (dynes sec/cm\^5) indicates improvement for this patient population.
Time frame: Baseline to Week 24
Population: Patients with measurements at Baseline and Week 24 were evaluated
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan Only | Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF) | Baseline | 761.2 dynes sec/cm^5 | Standard Deviation 306.57 |
| Ambrisentan Only | 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 |
| Placebo/Ambrisentan | Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF) | Week 24 | 439.8 dynes sec/cm^5 | Standard Deviation 130.34 |
| Placebo/Ambrisentan | Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF) | Baseline | 731.6 dynes sec/cm^5 | Standard Deviation 278.02 |
| Any Ambrisentan | Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF) | Baseline | 758.0 dynes sec/cm^5 | Standard Deviation 300.12 |
| Any Ambrisentan | Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF) | Week 24 | 509.8 dynes sec/cm^5 | Standard Deviation 190.18 |
| Any Placebo | Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF) | Baseline | 703.6 dynes sec/cm^5 | Standard Deviation 248.73 |
| Any Placebo | Change From Baseline in Pulmonary Vascular Resistance (PVR), Last Observation Carried Forward (LOCF) | Week 24 | 439.8 dynes sec/cm^5 | Standard Deviation 130.34 |
Comparison: Mean change from Baseline to Week 2495% CI: [-337.7, -160.2]
Comparison: Mean change from Baseline to Week 2495% CI: [-619.4, 35.78]
Comparison: Mean change from Baseline to Week 2495% CI: [-334.8, -172.8]
Comparison: Mean change from Baseline to Week 2495% CI: [-619.4, 35.78]
Secondary
Change From Baseline in Cardiac Output (LOCF)
This secondary hemodynamic outcome is supportive of the primary outcome. An increase in measurement value (L/min) indicates improvement for this patient population.
Time frame: Baseline to Week 24
Population: Patients with measurements at Baseline and Week 24 were evaluated
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan Only | Change From Baseline in Cardiac Output (LOCF) | Baseline | 4.4 L/min | Standard Deviation 1.22 |
| Ambrisentan Only | Change From Baseline in Cardiac Output (LOCF) | Week 24 | 5.2 L/min | Standard Deviation 1.27 |
| Placebo/Ambrisentan | Change From Baseline in Cardiac Output (LOCF) | Week 24 | 5.2 L/min | Standard Deviation 1.22 |
| Placebo/Ambrisentan | Change From Baseline in Cardiac Output (LOCF) | Baseline | 4.8 L/min | Standard Deviation 0.81 |
| Any Ambrisentan | Change From Baseline in Cardiac Output (LOCF) | Baseline | 4.4 L/min | Standard Deviation 1.17 |
| Any Ambrisentan | Change From Baseline in Cardiac Output (LOCF) | Week 24 | 5.2 L/min | Standard Deviation 1.24 |
| Any Placebo | Change From Baseline in Cardiac Output (LOCF) | Baseline | 4.8 L/min | Standard Deviation 0.71 |
| Any Placebo | Change From Baseline in Cardiac Output (LOCF) | Week 24 | 5.2 L/min | Standard Deviation 1.22 |
Comparison: Mean change from Baseline to Week 2495% CI: [0.43, 1.25]
Comparison: Mean change from Baseline to Week 2495% CI: [-0.77, 1.42]
Comparison: Mean change from Baseline to Week 2495% CI: [0.41, 1.15]
Comparison: Mean change from Baseline to Week 2495% CI: [-0.77, 1.42]
Secondary
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)
The primary analysis of this secondary outcome measure is mean percent change from Baseline to Week 24. The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated. A decrease in log-transformed measurement value (pg/mL) indicates improvement for this patient population.
Time frame: Baseline to Week 48
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan Only | 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 1.1 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Placebo/Ambrisentan | 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 | 5.9 pg/mL (log-transformed) | Standard Deviation 0.64 |
| Placebo/Ambrisentan | 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 | 6.4 pg/mL (log-transformed) | Standard Deviation 0.82 |
| Placebo/Ambrisentan | 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 | 6.7 pg/mL (log-transformed) | Standard Deviation 1.02 |
| Placebo/Ambrisentan | 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 | 6.3 pg/mL (log-transformed) | Standard Deviation 0.45 |
| Placebo/Ambrisentan | 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 | 6.0 pg/mL (log-transformed) | Standard Deviation 0.98 |
| Placebo/Ambrisentan | 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 | 6.2 pg/mL (log-transformed) | Standard Deviation 1.8 |
| Placebo Only | 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 | 7.6 pg/mL (log-transformed) | Standard Deviation 0 |
| Placebo Only | 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 | 8.0 pg/mL (log-transformed) | Standard Deviation 0 |
| Placebo Only | 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 | 0.0 pg/mL (log-transformed) | Standard Deviation 0 |
| Placebo Only | 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 | 7.6 pg/mL (log-transformed) | Standard Deviation 0 |
| Placebo Only | 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 | 7.5 pg/mL (log-transformed) | Standard Deviation 0 |
| Placebo Only | 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 | 8.0 pg/mL (log-transformed) | Standard Deviation 0 |
| Any Ambrisentan | 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 1.02 |
| Any Ambrisentan | 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 1.05 |
| Any Ambrisentan | 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 | 5.8 pg/mL (log-transformed) | Standard Deviation 0.99 |
| Any Ambrisentan | 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 | 5.7 pg/mL (log-transformed) | Standard Deviation 1.14 |
| Any Ambrisentan | 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 1.14 |
| Any Ambrisentan | 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 | 6.2 pg/mL (log-transformed) | Standard Deviation 1.1 |
| Any Placebo | 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 | 6.3 pg/mL (log-transformed) | Standard Deviation 1.08 |
| Any Placebo | 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 | 6.8 pg/mL (log-transformed) | Standard Deviation 0.8 |
| Any Placebo | 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 | 6.7 pg/mL (log-transformed) | Standard Deviation 1.46 |
| Any Placebo | 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 | 6.7 pg/mL (log-transformed) | Standard Deviation 1.01 |
| Any Placebo | 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 | 6.4 pg/mL (log-transformed) | Standard Deviation 1.12 |
| Any Placebo | 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 | 6.7 pg/mL (log-transformed) | Standard Deviation 1.02 |
Comparison: Mean change from Baseline to Week 4 (LOCF)
Comparison: Mean change from Baseline to Week 4 (LOCF)
Comparison: Mean change from Baseline to Week 4 (LOCF)
Comparison: Mean change from Baseline to Week 4 (LOCF)
Comparison: Mean change from Baseline to Week 12 (LOCF)
Comparison: Mean change from Baseline to Week 12 (LOCF)
Comparison: Mean change from Baseline to Week 12 (LOCF)
Comparison: Mean change from Baseline to Week 12 (LOCF)
Comparison: Mean change from Baseline to Week 24 (LOCF)
Comparison: Mean change from Baseline to Week 24 (LOCF)
Comparison: Mean change from Baseline to Week 24 (LOCF)
Comparison: Mean change from Baseline to Week 24 (LOCF)
Comparison: Mean change from Baseline to Week 36 (LOCF)
Comparison: Mean change from Baseline to Week 36 (LOCF)
Comparison: Mean change from Baseline to Week 36 (LOCF)
Comparison: Mean change from Baseline to Week 36 (LOCF)
Comparison: Mean change from Baseline to Week 48 (LOCF)
Comparison: Mean change from Baseline to Week 48 (LOCF)
Comparison: Mean change from Baseline to Week 48 (LOCF)
Comparison: Mean change from Baseline to Week 48 (LOCF)
Secondary
Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF)
This secondary hemodynamic outcome is supportive of the primary outcome. A decrease in measurement value (mmHg) indicates improvement for this patient population.
Time frame: Baseline to Week 24
Population: Patients with measurements at Baseline and Week 24 were evaluated
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan Only | Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF) | Baseline | 49.9 mmHg | Standard Deviation 9.75 |
| Ambrisentan Only | Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF) | Week 24 | 44.4 mmHg | Standard Deviation 10.95 |
| Placebo/Ambrisentan | Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF) | Week 24 | 38.8 mmHg | Standard Deviation 9.6 |
| Placebo/Ambrisentan | Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF) | Baseline | 54.5 mmHg | Standard Deviation 12.5 |
| Any Ambrisentan | Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF) | Week 24 | 43.8 mmHg | Standard Deviation 10.83 |
| Any Ambrisentan | Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF) | Baseline | 50.4 mmHg | Standard Deviation 9.98 |
| Any Placebo | Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF) | Baseline | 52.8 mmHg | Standard Deviation 11.48 |
| Any Placebo | Change From Baseline in Mean Pulmonary Artery Pressure (mPAP) (LOCF) | Week 24 | 38.8 mmHg | Standard Deviation 9.6 |
Comparison: Mean change from Baseline to Week 2495% CI: [-8.29, -2.46]
Comparison: Mean change from Baseline to Week 2495% CI: [-29.64, -1.86]
Comparison: Mean change from Baseline to Week 2495% CI: [-9.51, -3.61]
Comparison: Mean change from Baseline to Week 2495% CI: [-29.64, -1.86]
Secondary
Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF)
This secondary hemodynamic outcome is supportive of the primary outcome. A decrease in measurement value (mmHg) indicates improvement for this patient population.
Time frame: Baseline to Week 24
Population: Patients with measurements at Baseline and Week 24 were evaluated
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan Only | Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF) | Baseline | 8.5 mmHg | Standard Deviation 4.82 |
| Ambrisentan Only | Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF) | Week 24 | 8.4 mmHg | Standard Deviation 4.88 |
| Placebo/Ambrisentan | Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF) | Baseline | 10.3 mmHg | Standard Deviation 2.63 |
| Placebo/Ambrisentan | Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF) | Week 24 | 6.3 mmHg | Standard Deviation 1.71 |
| Any Ambrisentan | Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF) | Week 24 | 8.1 mmHg | Standard Deviation 4.66 |
| Any Ambrisentan | Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF) | Baseline | 8.7 mmHg | Standard Deviation 4.64 |
| Any Placebo | Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF) | Week 24 | 6.3 mmHg | Standard Deviation 1.71 |
| Any Placebo | Change From Baseline in Mean Right Atrial Pressure (mRAP) (LOCF) | Baseline | 11.1 mmHg | Standard Deviation 2.97 |
Comparison: Mean change from Baseline to Week 2495% CI: [-1.69, 1.56]
Comparison: Mean change from Baseline to Week 2495% CI: [-10.5, 2.5]
Comparison: Mean change from Baseline to Week 2495% CI: [-2.07, 1.04]
Comparison: Mean change from Baseline to Week 2495% CI: [-10.5, 2.5]
Secondary
Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
The primary analysis of this secondary outcome measure is mean change from Baseline to Week 24. The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated. An increase in measurement value (meters walked) indicates improvement for this patient population.
Time frame: Baseline to Week 48
Population: All enrolled Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Placebo/Ambrisentan | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Baseline | 433.3 meters walked | Standard Deviation 80.77 |
| Placebo/Ambrisentan | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 4 | 441.0 meters walked | Standard Deviation 83.88 |
| Placebo/Ambrisentan | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 12 | 435.8 meters walked | Standard Deviation 134.61 |
| Placebo/Ambrisentan | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 24 | 423.8 meters walked | Standard Deviation 110.05 |
| Placebo/Ambrisentan | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 36 | 399.3 meters walked | Standard Deviation 152.93 |
| Placebo/Ambrisentan | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 48 | 383.5 meters walked | Standard Deviation 192.47 |
| Placebo Only | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 12 | 422.0 meters walked | Standard Deviation 0 |
| Placebo Only | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 24 | 422.0 meters walked | Standard Deviation 0 |
| Placebo Only | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 36 | 402.0 meters walked | Standard Deviation 0 |
| Placebo Only | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Baseline | 335.0 meters walked | Standard Deviation 0 |
| Placebo Only | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 48 | 402.0 meters walked | Standard Deviation 0 |
| Placebo Only | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 4 | 442.0 meters walked | Standard Deviation 0 |
| Any Ambrisentan | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 48 | 379.4 meters walked | Standard Deviation 129.75 |
| Any Ambrisentan | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 4 | 383.7 meters walked | Standard Deviation 104.85 |
| Any Ambrisentan | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 36 | 370.2 meters walked | Standard Deviation 128.61 |
| Any Ambrisentan | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 24 | 387.0 meters walked | Standard Deviation 104.73 |
| Any Ambrisentan | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 12 | 384.3 meters walked | Standard Deviation 111.96 |
| Any Ambrisentan | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Baseline | 369.6 meters walked | Standard Deviation 98.56 |
| Any Placebo | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Baseline | 413.6 meters walked | Standard Deviation 82.61 |
| Any Placebo | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 36 | 399.8 meters walked | Standard Deviation 132.45 |
| Any Placebo | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 24 | 423.4 meters walked | Standard Deviation 95.31 |
| Any Placebo | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 48 | 387.2 meters walked | Standard Deviation 166.89 |
| Any Placebo | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 12 | 433.0 meters walked | Standard Deviation 116.74 |
| Any Placebo | Change From Baseline in Six Minute Walk Distance (6MWD) Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 4 | 441.2 meters walked | Standard Deviation 72.65 |
Comparison: Mean change from Baseline to Week 4 (LOCF)95% CI: [-3.9, 28.4]
Comparison: Mean change from Baseline to Week 4 (LOCF)95% CI: [-26, 41.5]
Comparison: Mean change from Baseline to Week 4 (LOCF)
Comparison: Mean change from Baseline to Week 4 (LOCF)95% CI: [-2.7, 26.2]
Comparison: Mean change from Baseline to Week 4 (LOCF)95% CI: [-32, 87.2]
Comparison: Mean change from Baseline to Week 12 (LOCF)95% CI: [-1.4, 28.5]
Comparison: Mean change from Baseline to Week 12 (LOCF)95% CI: [-91.5, 96.5]
Comparison: Mean change from Baseline to Week 12 (LOCF)
Comparison: Mean change from Baseline to Week 12 (LOCF)95% CI: [-2.1, 26.9]
Comparison: Mean change from Baseline to Week 12 (LOCF)95% CI: [-59.6, 98.4]
Comparison: Mean change from Baseline to Week 24 (LOCF)95% CI: [0.5, 35.6]
Comparison: Mean change from Baseline to Week 24 (LOCF)95% CI: [-56.5, 37.5]
Comparison: Mean change from Baseline to Week 24 (LOCF)
Comparison: Mean change from Baseline to Week 24 (LOCF)95% CI: [-1, 31.1]
Comparison: Mean change from Baseline to Week 24 (LOCF)95% CI: [-52.5, 72.1]
Comparison: Mean change from Baseline to Week 36 (LOCF)95% CI: [-25.6, 30.1]
Comparison: Mean change from Baseline to Week 36 (LOCF)95% CI: [-182.2, 114.2]
Comparison: Mean change from Baseline to Week 36 (LOCF)
Comparison: Mean change from Baseline to Week 36 (LOCF)95% CI: [-28.4, 24.8]
Comparison: Mean change from Baseline to Week 36 (LOCF)95% CI: [-128.6, 101]
Comparison: Mean change from Baseline to Week 48 (LOCF)95% CI: [-15, 44.2]
Comparison: Mean change from Baseline to Week 48 (LOCF)95% CI: [-251.4, 151.9]
Comparison: Mean change from Baseline to Week 48 (LOCF)
Comparison: Mean change from Baseline to Week 48 (LOCF)95% CI: [-22.4, 37.3]
Comparison: Mean change from Baseline to Week 48 (LOCF)95% CI: [-177.3, 124.5]
Secondary
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)
The primary analysis of this secondary outcome measure is mean change from Baseline to Week 24. The changes from Baseline to Weeks 12, 36, and 48 were also evaluated. Lower scores and decreases from baseline represent improved functioning and QOL. The CAMPHOR survey was not assessed at Week 4. The total CAMPHOR score scale ranges from 0 (good) to 25 (poor). A reduction in score over time represents improvement in this patient population.
Time frame: Baseline to Week 48
Population: All enrolled Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 6.1 |
| Placebo/Ambrisentan | 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 | 5.5 units on a scale | Standard Deviation 3.11 |
| Placebo/Ambrisentan | 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 | 3.0 units on a scale | Standard Deviation 2.94 |
| Placebo/Ambrisentan | 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 | 3.5 units on a scale | Standard Deviation 3.7 |
| Placebo/Ambrisentan | 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 | 4.3 units on a scale | Standard Deviation 5.44 |
| Placebo/Ambrisentan | 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 | 3.8 units on a scale | Standard Deviation 3.5 |
| Placebo Only | 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 | 3.0 units on a scale | Standard Deviation 0 |
| Placebo Only | 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 | 4.0 units on a scale | Standard Deviation 0 |
| Placebo Only | 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 | 2.0 units on a scale | Standard Deviation 0 |
| Placebo Only | 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 | 2.0 units on a scale | Standard Deviation 0 |
| Placebo Only | 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 | 3.0 units on a scale | Standard Deviation 0 |
| Any Ambrisentan | 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 | 7.1 units on a scale | Standard Deviation 6.63 |
| Any Ambrisentan | 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 | 6.7 units on a scale | Standard Deviation 5.32 |
| Any Ambrisentan | 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 | 7.2 units on a scale | Standard Deviation 5.98 |
| Any Ambrisentan | 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 | 7.7 units on a scale | Standard Deviation 6.12 |
| Any Ambrisentan | 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 | 6.7 units on a scale | Standard Deviation 5.69 |
| Any Placebo | 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 | 4.8 units on a scale | Standard Deviation 3.11 |
| Any Placebo | 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 | 2.8 units on a scale | Standard Deviation 2.59 |
| Any Placebo | 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 | 3.4 units on a scale | Standard Deviation 3.21 |
| Any Placebo | 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 | 4.2 units on a scale | Standard Deviation 4.71 |
| Any Placebo | 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 | 3.6 units on a scale | Standard Deviation 3.05 |
Comparison: Mean change from Baseline to Week 12 (LOCF)95% CI: [-2.7, 0.4]
Comparison: Mean change from Baseline to Week 12 (LOCF)95% CI: [-6.5, 9]
Comparison: Mean change from Baseline to Week 12 (LOCF)
Comparison: Mean change from Baseline to Week 12 (LOCF)95% CI: [-2.3, 0.6]
Comparison: Mean change from Baseline to Week 12 (LOCF)95% CI: [-4.9, 6.1]
Comparison: Mean change from Baseline to Week 24 (LOCF)95% CI: [-2.7, 1.1]
Comparison: Mean change from Baseline to Week 24 (LOCF)95% CI: [-7.7, 5.2]
Comparison: Mean change from Baseline to Week 24 (LOCF)
Comparison: Mean change from Baseline to Week 24 (LOCF)95% CI: [-2.6, 0.9]
Comparison: Mean change from Baseline to Week 24 (LOCF)95% CI: [-5.8, 3]
Comparison: Mean change from Baseline to Week 36 (LOCF)95% CI: [-2.3, 1.7]
Comparison: Mean change from Baseline to Week 36 (LOCF)95% CI: [-8.1, 6.6]
Comparison: Mean change from Baseline to Week 36 (LOCF)
Comparison: Mean change from Baseline to Week 36 (LOCF)95% CI: [-2.2, 1.5]
Comparison: Mean change from Baseline to Week 36 (LOCF)95% CI: [-5.8, 4.2]
Comparison: Mean change from Baseline to Week 48 (LOCF)95% CI: [-2.8, 2.1]
Comparison: Mean change from Baseline to Week 48 (LOCF)95% CI: [-11.4, 10.4]
Comparison: Mean change from Baseline to Week 48 (LOCF)
Comparison: Mean change from Baseline to Week 48 (LOCF)95% CI: [-2.7, 1.9]
Comparison: Mean change from Baseline to Week 48 (LOCF)95% CI: [-8, 6.8]
Secondary
Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48.
The primary analysis of this secondary outcome measure is change from Baseline to Week 24. The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated. WHO categories are 1 to 4 with the worst category being 4. Improvement is represented by a change in category to a lower number (for example, change from category 3 to 2), and deterioration is represented by a change in category to a higher number (for example, change from category 2 to 4). No change is represented by no change in category (for example, category 2 which remains 2).
Time frame: Baseline to Week 48
Population: All enrolled Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 12 - Missing Data | 0 participants |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 24 - Missing Data | 0 participants |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 36 - Missing Data | 0 participants |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 24 - Improvement | 2 participants |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 36 - No Change | 2 participants |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 12 - Improvement | 1 participants |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 24 - Deterioration | 0 participants |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 48 - Missing Data | 0 participants |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 24 - No Change | 2 participants |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 48 - Deterioration | 0 participants |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 36 - Improvement | 2 participants |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 36 - Deterioration | 0 participants |
| Placebo/Ambrisentan | 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 |
| Placebo/Ambrisentan | 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 |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 4 - Improvement | 0 participants |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 12 - No Change | 3 participants |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 48 - Improvement | 1 participants |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 4 - No Change | 4 participants |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 4 - Missing Data | 0 participants |
| Placebo/Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 48 - No Change | 3 participants |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 12 - Improvement | 1 participants |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 4 - Improvement | 1 participants |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 4 - No Change | 0 participants |
| Placebo Only | 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 |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 4 - Missing Data | 0 participants |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 24 - Deterioration | 0 participants |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 12 - No Change | 0 participants |
| Placebo Only | 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 |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 12 - Missing Data | 0 participants |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 24 - Improvement | 1 participants |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 24 - No Change | 0 participants |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 24 - Missing Data | 0 participants |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 36 - Improvement | 1 participants |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 36 - No Change | 0 participants |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 36 - Deterioration | 0 participants |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 36 - Missing Data | 0 participants |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 48 - Improvement | 1 participants |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 48 - No Change | 0 participants |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 48 - Deterioration | 0 participants |
| Placebo Only | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 48 - Missing Data | 0 participants |
| Any Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 36 - Improvement | 19 participants |
| Any Ambrisentan | 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 |
| Any Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 12 - No Change | 27 participants |
| Any Ambrisentan | 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 |
| Any Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 48 - Improvement | 15 participants |
| Any Ambrisentan | 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 |
| Any Ambrisentan | 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 |
| Any Ambrisentan | 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 |
| Any Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 48 - No Change | 20 participants |
| Any Ambrisentan | 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 |
| Any Ambrisentan | 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 |
| Any Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 12 - Improvement | 9 participants |
| Any Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 24 - No Change | 21 participants |
| Any Ambrisentan | 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 |
| Any Ambrisentan | 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 |
| Any Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 36 - No Change | 16 participants |
| Any Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 24 - Improvement | 14 participants |
| Any Ambrisentan | 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 |
| Any Ambrisentan | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 4 - No Change | 33 participants |
| Any Ambrisentan | 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 |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 36 - Missing Data | 0 participants |
| Any Placebo | 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 |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 36 - Improvement | 3 participants |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 12 - No Change | 3 participants |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 36 - No Change | 2 participants |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 12 - Improvement | 2 participants |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 48 - Deterioration | 0 participants |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 36 - Deterioration | 0 participants |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 4 - Missing Data | 0 participants |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 4 - Improvement | 1 participants |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 24 - Missing Data | 0 participants |
| Any Placebo | 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 |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 48 - Improvement | 2 participants |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 48 - Missing Data | 0 participants |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 48 - No Change | 3 participants |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 4 - No Change | 4 participants |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 24 - No Change | 2 participants |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 24 - Improvement | 3 participants |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 24 - Deterioration | 0 participants |
| Any Placebo | Change From Baseline in World Health Organization (WHO) Functional Class (LOCF) Measured at Weeks 4, 12, 24, 36 and 48. | Week 12 - Missing Data | 0 participants |
Secondary
Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF)
The primary analysis of this secondary outcome measure is mean change from Baseline to Week 24. The changes from Baseline to Weeks 4, 12, 36, and 48 were also evaluated. The dyspnea index measures the degree of breathlessness after completion of the 6MWT using a scale of 0 to 10, with 0 indicating no breathlessness and 10 indicating maximum breathlessness.
Time frame: Baseline to Week 48
Population: All enrolled Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Ambrisentan Only | 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 |
| Placebo/Ambrisentan | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 4 | 3.3 units on a scale | Standard Deviation 2.22 |
| Placebo/Ambrisentan | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 36 | 3.5 units on a scale | Standard Deviation 2.65 |
| Placebo/Ambrisentan | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 24 | 1.9 units on a scale | Standard Deviation 1.31 |
| Placebo/Ambrisentan | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 48 | 3.5 units on a scale | Standard Deviation 4.04 |
| Placebo/Ambrisentan | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Baseline | 2.5 units on a scale | Standard Deviation 1.29 |
| Placebo/Ambrisentan | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 12 | 4.0 units on a scale | Standard Deviation 2.83 |
| Placebo Only | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 36 | 3.0 units on a scale | Standard Deviation 0 |
| Placebo Only | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 48 | 3.0 units on a scale | Standard Deviation 0 |
| Placebo Only | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Baseline | 3.0 units on a scale | Standard Deviation 0 |
| Placebo Only | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 4 | 2.0 units on a scale | Standard Deviation 0 |
| Placebo Only | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 12 | 3.0 units on a scale | Standard Deviation 0 |
| Placebo Only | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 24 | 3.0 units on a scale | Standard Deviation 0 |
| Any Ambrisentan | 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 |
| Any Ambrisentan | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 24 | 2.8 units on a scale | Standard Deviation 1.91 |
| Any Ambrisentan | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 4 | 3.2 units on a scale | Standard Deviation 1.71 |
| Any Ambrisentan | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Baseline | 3.6 units on a scale | Standard Deviation 2.03 |
| Any Ambrisentan | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 48 | 3.1 units on a scale | Standard Deviation 2.49 |
| Any Ambrisentan | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 12 | 3.3 units on a scale | Standard Deviation 2.02 |
| Any Placebo | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 48 | 3.4 units on a scale | Standard Deviation 3.51 |
| Any Placebo | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Baseline | 2.6 units on a scale | Standard Deviation 1.14 |
| Any Placebo | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 12 | 3.8 units on a scale | Standard Deviation 2.49 |
| Any Placebo | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 24 | 2.1 units on a scale | Standard Deviation 1.24 |
| Any Placebo | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 36 | 3.4 units on a scale | Standard Deviation 2.3 |
| Any Placebo | Change in Dyspnea Index Measured at Weeks 4, 12, 24, 36 and 48 (LOCF) | Week 4 | 3.0 units on a scale | Standard Deviation 2 |
Comparison: Mean change from Baseline to Week 4 (LOCF)95% CI: [-0.9, 0.1]
Comparison: Mean change from Baseline to Week 4 (LOCF)95% CI: [-1.1, 0]
Comparison: Mean change from Baseline to Week 4 (LOCF)95% CI: [-1.6, 3.1]
Comparison: Mean change from Baseline to Week 4 (LOCF)
Comparison: Mean change from Baseline to Week 4 (LOCF)95% CI: [-1.5, 2.3]
Comparison: Mean change from Baseline to Week 12 (LOCF)95% CI: [-1.1, 0]
Comparison: Mean change from Baseline to Week 12 (LOCF)95% CI: [-2.3, 5.3]
Comparison: Mean change from Baseline to Week 12 (LOCF)
Comparison: Mean change from Baseline to Week 12 (LOCF)95% CI: [-0.9, 0.2]
Comparison: Mean change from Baseline to Week 12 (LOCF)95% CI: [-1.5, 3.9]
Comparison: Mean change from Baseline to Week 24 (LOCF)95% CI: [-1.5, -0.2]
Comparison: Mean change from Baseline to Week 24 (LOCF)95% CI: [-1.8, 0.6]
Comparison: Mean change from Baseline to Week 24 (LOCF)
Comparison: Mean change from Baseline to Week 24 (LOCF)95% CI: [-1.4, -0.3]
Comparison: Mean change from Baseline to Week 24 (LOCF)95% CI: [-1.4, 0.4]
Comparison: Mean change from Baseline to Week 36 (LOCF)95% CI: [-1.2, 0.1]
Comparison: Mean change from Baseline to Week 36 (LOCF)95% CI: [-2.2, 4.2]
Comparison: Mean change from Baseline to Week 36 (LOCF)
Comparison: Mean change from Baseline to Week 36 (LOCF)95% CI: [-1, 0.2]
Comparison: Mean change from Baseline to Week 36 (LOCF)95% CI: [-1.4, 3]
Comparison: Mean change from Baseline to Week 48 (LOCF)95% CI: [-1.4, 0.1]
Comparison: Mean change from Baseline to Week 48 (LOCF)95% CI: [-4.5, 6.5]
Comparison: Mean change from Baseline to Week 48 (LOCF)
Comparison: Mean change from Baseline to Week 48 (LOCF)95% CI: [-1.3, 0.3]
Comparison: Mean change from Baseline to Week 48 (LOCF)95% CI: [-3, 4.6]
Secondary
Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48
Overall survival was defined as the time from initiation of active treatment to death. Results are presented as the Kaplan-Meier estimate (% probability) of death after a given time.
Time frame: Baseline to Week 48+
Population: The Ambrisentan Only and Any Ambrisentan Groups were analyzed for Overall Survival
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Placebo/Ambrisentan | Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 | After Week 48 | 3 Probability of death occurring (%) |
| Placebo/Ambrisentan | 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 (%) |
| Placebo/Ambrisentan | 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 (%) |
| Placebo/Ambrisentan | 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 (%) |
| Placebo/Ambrisentan | 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 (%) |
| Placebo/Ambrisentan | 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 (%) |
| Placebo/Ambrisentan | 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 (%) |
| Placebo/Ambrisentan | 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 (%) |
| Placebo/Ambrisentan | 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 (%) |
| Placebo/Ambrisentan | Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 | At Week 40 | 3 Probability of death occurring (%) |
| Placebo/Ambrisentan | Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 | At Week 44 | 3 Probability of death occurring (%) |
| Placebo/Ambrisentan | Overall Survival, Evaluated at Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and After Week 48 | At Week 48 | 3 Probability of death occurring (%) |
| Placebo/Ambrisentan | 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 (%) |
Secondary
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
The time to clinical worsening was defined as the time from enrollment to the first occurrence of death, lung transplantation, hospitalization for PAH, atrial septostomy, or initiation of chronic parenteral prostanoid therapy. Results are presented as the Kaplan-Meier estimate (% probability) of having clinical worsening after a given time.
Time frame: Baseline to Week 48+
Population: The Ambrisentan Only and Any Ambrisentan Groups were analyzed for Time to Clinical Worsening
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Ambrisentan Only | 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 (%) |
| Placebo/Ambrisentan | 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 | 17 Probability of clinical worsening (%) |
| Placebo/Ambrisentan | 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 (%) |
| Placebo/Ambrisentan | 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 (%) |
| Placebo/Ambrisentan | 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 (%) |
| Placebo/Ambrisentan | 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 (%) |
| Placebo/Ambrisentan | 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 (%) |
| Placebo/Ambrisentan | 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 (%) |
| Placebo/Ambrisentan | 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 | 14 Probability of clinical worsening (%) |
| Placebo/Ambrisentan | 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 | 14 Probability of clinical worsening (%) |
| Placebo/Ambrisentan | 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 | 17 Probability of clinical worsening (%) |
| Placebo/Ambrisentan | 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 | 17 Probability of clinical worsening (%) |
| Placebo/Ambrisentan | 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 | 17 Probability of clinical worsening (%) |
| Placebo/Ambrisentan | 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 (%) |