Pulmonary Arterial Hypertension, Pulmonary Hypertension
Conditions
Keywords
endothelin receptor antagonist (ETRA), Sitaxsentan
Brief summary
As monotherapy for pulmonary arterial hypertension (PAH) begins to fail additional therapies are introduced. Although co-administration of sitaxsentan and sildenafil is well tolerated the controlled safety/efficacy database of the combination is limited.
Interventions
DRUGSitaxsentan
Sitaxsentan = 100 mg tablet administered orally, once daily Sildenafil placebo = 1 tablet administered orally, three times a day
Sitaxsentan = 100 mg tablet administered orally, once daily plus Sildenafil = 20 mg tablet administered orally, three times a day
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
16 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Previously enrolled in B1321001 (NCT00795639) and completed the 12-week study as planned.
Exclusion criteria
* Treated with an investigational drug, other than sitaxsentan sodium in B1321001 (NCT00795639), or device that has not received regulatory approval within the 30 days prior to Baseline/Day 1 or during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Clinical Worsening (TTCW) | Baseline, Weeks 12, 24 or Early Termination (ET) | Clinical worsening defined as time between first dose of study drug and occurrence of death; or heart-lung/lung transplant; or hospitalization for worsening pulmonary atrial hypertension (PAH); or atrial septostomy; or withdrawal due to addition of chronic medications for treatment of worsening PAH: prostacyclin/prostacyclin analogues/phosphodiesterase-5inhibitors/alternative endothelin receptor antagonists/intravenous inotropes; or increase of calcium channel blockers or oxygen. TTCW measured as duration between study's first dose date in and date when first clinical worsening event occurs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Weeks 12, 24, 48 | Baseline, Weeks 12, 24 or ET | WHO PAH Functional Classification of physical activity limitations: I (no limitation), II (slight limitation), III (marked limitations, comfortable at rest) and IV (unable to carry out any physical activity without symptoms). The change from baseline in WHO class was classified as Improved (decrease in functional class), No Change (functional class stayed the same), and Worsened (functional class increased). The change from baseline in WHO functional class at Week X was summarized with frequency count and percentage in each category based on imputed data for missing values at Week X. |
| Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Physical Functioning Domain | Baseline, Weeks 12, 24 and ET | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Physical Functioning score at Week x minus score at baseline. |
| Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitations Due to Physical Health Problems Domain | Baseline, Weeks 12, 24 or ET | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Role Limitations Due to Physical Health Problems score at Week x minus score at baseline. |
| Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Bodily Pain Domain | Baseline, Weeks 12, 24 or ET | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Bodily Pain score at Week x minus score at baseline. |
| Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - General Health Domain | Baseline, Weeks 12, 24 or ET | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = General Health score at Week x minus score at baseline. |
| Change From Baseline in the Total Distance Walked During 6 Minute Walk Distance (6MWD) | Baseline to Weeks 12 and 24 | 6 MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Continuous pulse oximetry was conducted during the test for safety. Change from baseline = score at Week x - score at baseline. |
| Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Social Functioning Domain | Baseline, Weeks 12, 24 or ET | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Social Functioning score at Week x minus score at baseline. |
| Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitation Due to Emotional Problems Domain | Baseline, Weeks 12, 24 or ET | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Role Limitations Due to Emotional Problems score at Week x minus score at baseline. |
| Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Mental Health Domain | Baseline, Weeks 12, 24 or ET | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Mental Health score at Week x minus score at baseline. |
| Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Mental Health | Baseline, Weeks 12, 24 or ET | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Composite Mental Health score at Week x minus score at baseline. |
| Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Physical Health | Baseline, Weeks 12, 24 or ET | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Composite Physical Health score at Week x minus score at baseline. |
| Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Vitality Domain | Baseline, Weeks 12, 24 or ET | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Vitality score at Week x minus score at baseline. |
Countries
Argentina, Bulgaria, Chile, China, Colombia, Czechia, India, Malaysia, Mexico, Peru, Romania, Russia, Serbia, South Africa, Thailand, Turkey (Türkiye), Ukraine, United States
Participant flow
Pre-assignment details
Participants who successfully completed treatment in study B1321001 (NCT00795639).
Participants by arm
| Arm | Count |
|---|---|
| Sitaxsentan and Placebo Sitaxsentan sodium (100 milligrams \[mg\]) orally once daily and placebo orally three times a day (TID) | 67 |
| Sitaxsentan and Sildenafil Sitaxsentan sodium (100 mg) orally once daily and sildenafil citrate (20 mg) TID | 64 |
| Total | 131 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 5 |
| Overall Study | Death | 2 | 4 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Randomized and not treated | 1 | 0 |
| Overall Study | Terminated by sponsor | 53 | 55 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Sitaxsentan and Placebo | Total | Sitaxsentan and Sildenafil |
|---|---|---|---|
| Age, Customized 18-44 years | 38 participants | 79 participants | 41 participants |
| Age, Customized 45-64 years | 20 participants | 38 participants | 18 participants |
| Age, Customized >= 65 years | 8 participants | 13 participants | 5 participants |
| Age, Customized less than 18 years | 1 participants | 1 participants | 0 participants |
| Sex: Female, Male Female | 55 Participants | 104 Participants | 49 Participants |
| Sex: Female, Male Male | 12 Participants | 27 Participants | 15 Participants |
| World Health Organization (WHO) Functional Classification Functional Class I | 0 number | 0 number | 0 number |
| World Health Organization (WHO) Functional Classification Functional Class II | 12 number | 23 number | 11 number |
| World Health Organization (WHO) Functional Classification Functional Class III | 55 number | 107 number | 52 number |
| World Health Organization (WHO) Functional Classification Functional Class IV | 0 number | 1 number | 1 number |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 26 / 66 | 28 / 64 |
| serious Total, serious adverse events | 14 / 66 | 15 / 64 |
Outcome results
Primary
Time to Clinical Worsening (TTCW)
Clinical worsening defined as time between first dose of study drug and occurrence of death; or heart-lung/lung transplant; or hospitalization for worsening pulmonary atrial hypertension (PAH); or atrial septostomy; or withdrawal due to addition of chronic medications for treatment of worsening PAH: prostacyclin/prostacyclin analogues/phosphodiesterase-5inhibitors/alternative endothelin receptor antagonists/intravenous inotropes; or increase of calcium channel blockers or oxygen. TTCW measured as duration between study's first dose date in and date when first clinical worsening event occurs.
Time frame: Baseline, Weeks 12, 24 or Early Termination (ET)
Population: Intent-to-Treat population (ITT): all participants who were randomized
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sitaxsentan and Placebo | Time to Clinical Worsening (TTCW) | NA Days |
| Sitaxsentan and Sildenafil | Time to Clinical Worsening (TTCW) | NA Days |
p-value: 0.541695% CI: [0.602, 1.233]Log Rank
Secondary
Change From Baseline in the Total Distance Walked During 6 Minute Walk Distance (6MWD)
6 MWD was the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Continuous pulse oximetry was conducted during the test for safety. Change from baseline = score at Week x - score at baseline.
Time frame: Baseline to Weeks 12 and 24
Population: ITT; N=number of participants analyzed; Missing values at Weeks 12 and 24 imputed with the last non-missing 6MWD based on the last observation carried forward (LOCF) method
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan and Placebo | Change From Baseline in the Total Distance Walked During 6 Minute Walk Distance (6MWD) | Baseline | 350.9 meters (m) | Standard Deviation 74.47 |
| Sitaxsentan and Placebo | Change From Baseline in the Total Distance Walked During 6 Minute Walk Distance (6MWD) | Change at Week 12 | -6.9 meters (m) | Standard Deviation 71 |
| Sitaxsentan and Placebo | Change From Baseline in the Total Distance Walked During 6 Minute Walk Distance (6MWD) | Change at Week 24 | -5.4 meters (m) | Standard Deviation 62.74 |
| Sitaxsentan and Sildenafil | Change From Baseline in the Total Distance Walked During 6 Minute Walk Distance (6MWD) | Baseline | 354.7 meters (m) | Standard Deviation 79.88 |
| Sitaxsentan and Sildenafil | Change From Baseline in the Total Distance Walked During 6 Minute Walk Distance (6MWD) | Change at Week 12 | 23.2 meters (m) | Standard Deviation 56.49 |
| Sitaxsentan and Sildenafil | Change From Baseline in the Total Distance Walked During 6 Minute Walk Distance (6MWD) | Change at Week 24 | 17.5 meters (m) | Standard Deviation 66.84 |
Comparison: Baseline to Week 12p-value: 0.0049ANCOVA
Secondary
Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Weeks 12, 24, 48
WHO PAH Functional Classification of physical activity limitations: I (no limitation), II (slight limitation), III (marked limitations, comfortable at rest) and IV (unable to carry out any physical activity without symptoms). The change from baseline in WHO class was classified as Improved (decrease in functional class), No Change (functional class stayed the same), and Worsened (functional class increased). The change from baseline in WHO functional class at Week X was summarized with frequency count and percentage in each category based on imputed data for missing values at Week X.
Time frame: Baseline, Weeks 12, 24 or ET
Population: ITT
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sitaxsentan and Placebo | Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Weeks 12, 24, 48 | Week 12 Improvement | 14 participant |
| Sitaxsentan and Placebo | Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Weeks 12, 24, 48 | Week 12 No Change | 52 participant |
| Sitaxsentan and Placebo | Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Weeks 12, 24, 48 | Week 12 Deterioration | 1 participant |
| Sitaxsentan and Placebo | Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Weeks 12, 24, 48 | Week 24 Improvement | 13 participant |
| Sitaxsentan and Placebo | Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Weeks 12, 24, 48 | Week 24 No Change | 53 participant |
| Sitaxsentan and Placebo | Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Weeks 12, 24, 48 | Week 24 Deterioration | 1 participant |
| Sitaxsentan and Sildenafil | Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Weeks 12, 24, 48 | Week 24 No Change | 47 participant |
| Sitaxsentan and Sildenafil | Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Weeks 12, 24, 48 | Week 12 Improvement | 14 participant |
| Sitaxsentan and Sildenafil | Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Weeks 12, 24, 48 | Week 24 Improvement | 16 participant |
| Sitaxsentan and Sildenafil | Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Weeks 12, 24, 48 | Week 12 No Change | 49 participant |
| Sitaxsentan and Sildenafil | Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Weeks 12, 24, 48 | Week 24 Deterioration | 1 participant |
| Sitaxsentan and Sildenafil | Change From Baseline in World Health Organization (WHO) Functional Class in Participants With PAH at Weeks 12, 24, 48 | Week 12 Deterioration | 1 participant |
Comparison: Baseline to Week 12p-value: 0.8223Cochran-Mantel-Haenszel
Secondary
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Bodily Pain Domain
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Bodily Pain score at Week x minus score at baseline.
Time frame: Baseline, Weeks 12, 24 or ET
Population: ITT; N=number of participants analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Bodily Pain Domain | Baseline | 46.9 units on a scale | Standard Deviation 10.19 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Bodily Pain Domain | Change at Week 12 | -0.7 units on a scale | Standard Deviation 7.96 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Bodily Pain Domain | Change at Week 24 | -1.6 units on a scale | Standard Deviation 8.04 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Bodily Pain Domain | Baseline | 45.1 units on a scale | Standard Deviation 10.37 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Bodily Pain Domain | Change at Week 12 | 3.1 units on a scale | Standard Deviation 9.91 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Bodily Pain Domain | Change at Week 24 | 0.8 units on a scale | Standard Deviation 9.86 |
Comparison: Baseline to Week 1295% CI: [-3.78, 2.04]
Comparison: Baseline to Week 1295% CI: [-0.41, 4.9]
Comparison: Baseline to Week 12p-value: 0.0624ANCOVA
Secondary
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Mental Health
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Composite Mental Health score at Week x minus score at baseline.
Time frame: Baseline, Weeks 12, 24 or ET
Population: ITT; N=number of participants analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Mental Health | Baseline | 45.1 units on a scale | Standard Deviation 11.98 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Mental Health | Change at Week 12 | -0.4 units on a scale | Standard Deviation 8.67 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Mental Health | Change at Week 24 | 0.3 units on a scale | Standard Deviation 8.45 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Mental Health | Baseline | 43.9 units on a scale | Standard Deviation 11.29 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Mental Health | Change at Week 12 | 1.6 units on a scale | Standard Deviation 9.36 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Mental Health | Change at Week 24 | -0.6 units on a scale | Standard Deviation 10.16 |
Comparison: Baseline to Week 1295% CI: [0.37, 5.05]
Comparison: Baseline to Week 1295% CI: [-1.21, 3.58]
Comparison: Baseline to Week 12p-value: 0.2897ANCOVA
Secondary
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Physical Health
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Composite Physical Health score at Week x minus score at baseline.
Time frame: Baseline, Weeks 12, 24 or ET
Population: ITT; N=number of participants analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Physical Health | Baseline | 39.7 units on a scale | Standard Deviation 8.01 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Physical Health | Change at Week 12 | -0.1 units on a scale | Standard Deviation 6.79 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Physical Health | Change at Week 24 | -0.1 units on a scale | Standard Deviation 6.49 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Physical Health | Baseline | 39.1 units on a scale | Standard Deviation 7.97 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Physical Health | Change at Week 12 | 2.4 units on a scale | Standard Deviation 5.54 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Composite Physical Health | Change at Week 24 | 3.1 units on a scale | Standard Deviation 6.34 |
Comparison: Baseline to Week 1295% CI: [-2.05, 1.38]
Comparison: Baseline to Week 1295% CI: [0.46, 3.82]
Comparison: Baseline to Week 12p-value: 0.0179ANCOVA
Secondary
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - General Health Domain
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = General Health score at Week x minus score at baseline.
Time frame: Baseline, Weeks 12, 24 or ET
Population: ITT; N=number of participants analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - General Health Domain | Change at Week 12 | -0.5 units on a scale | Standard Deviation 6.73 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - General Health Domain | Change at Week 24 | 0.5 units on a scale | Standard Deviation 7.68 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - General Health Domain | Baseline | 38.8 units on a scale | Standard Deviation 9.69 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - General Health Domain | Change at Week 12 | 2.1 units on a scale | Standard Deviation 7.86 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - General Health Domain | Baseline | 38.9 units on a scale | Standard Deviation 9.35 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - General Health Domain | Change at Week 24 | 2.8 units on a scale | Standard Deviation 9.1 |
Comparison: Baseline to Week 1295% CI: [-2.57, 2.06]
Comparison: Baseline to Week 1295% CI: [0.48, 4.82]
Comparison: Baseline to Week 12p-value: 0.0324ANCOVA
Secondary
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Mental Health Domain
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Mental Health score at Week x minus score at baseline.
Time frame: Baseline, Weeks 12, 24 or ET
Population: ITT; N=number of participants analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Mental Health Domain | Baseline | 45.0 units on a scale | Standard Deviation 11.6 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Mental Health Domain | Change at Week 12 | 0.2 units on a scale | Standard Deviation 9.65 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Mental Health Domain | Change at Week 24 | 1.6 units on a scale | Standard Deviation 9.26 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Mental Health Domain | Baseline | 44.5 units on a scale | Standard Deviation 11.5 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Mental Health Domain | Change at Week 12 | 2.5 units on a scale | Standard Deviation 10.92 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Mental Health Domain | Change at Week 24 | 1.3 units on a scale | Standard Deviation 11.6 |
Comparison: Baseline to Week 1295% CI: [-1.61, 4.5]
Comparison: Baseline to Week 1295% CI: [0.82, 6.5]
Comparison: Baseline to Week 12p-value: 0.2087ANCOVA
Secondary
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Physical Functioning Domain
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Physical Functioning score at Week x minus score at baseline.
Time frame: Baseline, Weeks 12, 24 and ET
Population: ITT; N=number of participants analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Physical Functioning Domain | Baseline | 37.7 units on a scale | Standard Deviation 8.95 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Physical Functioning Domain | Change at Week 12 | -0.3 units on a scale | Standard Deviation 6.97 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Physical Functioning Domain | Change at Week 24 | 0.7 units on a scale | Standard Deviation 6.78 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Physical Functioning Domain | Baseline | 37.0 units on a scale | Standard Deviation 9.95 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Physical Functioning Domain | Change at Week 12 | 2.9 units on a scale | Standard Deviation 6.26 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Physical Functioning Domain | Change at Week 24 | 3.7 units on a scale | Standard Deviation 8.16 |
Comparison: Baseline to Week 1295% CI: [-3.13, 1.2]
Comparison: Baseline to Week 1295% CI: [0.31, 4.36]
Comparison: Baseline to Week 12p-value: 0.0094ANCOVA
Secondary
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitation Due to Emotional Problems Domain
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Role Limitations Due to Emotional Problems score at Week x minus score at baseline.
Time frame: Baseline, Weeks 12, 24 or ET
Population: ITT; N=number of participants analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitation Due to Emotional Problems Domain | Baseline | 40.1 units on a scale | Standard Deviation 12.3 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitation Due to Emotional Problems Domain | Change at Week 12 | -1.9 units on a scale | Standard Deviation 10.91 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitation Due to Emotional Problems Domain | Change at Week 24 | -0.5 units on a scale | Standard Deviation 9.72 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitation Due to Emotional Problems Domain | Baseline | 37.7 units on a scale | Standard Deviation 11.28 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitation Due to Emotional Problems Domain | Change at Week 12 | 0.9 units on a scale | Standard Deviation 8.84 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitation Due to Emotional Problems Domain | Change at Week 24 | -1.2 units on a scale | Standard Deviation 10.09 |
Comparison: Baseline to Week 1295% CI: [-3.09, 3.18]
Comparison: Baseline to Week 1295% CI: [-0.62, 5.16]
Comparison: Baseline to Week 12p-value: 0.2161ANCOVA
Secondary
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitations Due to Physical Health Problems Domain
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Role Limitations Due to Physical Health Problems score at Week x minus score at baseline.
Time frame: Baseline, Weeks 12, 24 or ET
Population: ITT; N=number of participants analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitations Due to Physical Health Problems Domain | Baseline | 37.9 units on a scale | Standard Deviation 10.21 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitations Due to Physical Health Problems Domain | Change at Week 12 | -2.2 units on a scale | Standard Deviation 9.72 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitations Due to Physical Health Problems Domain | Change at Week 24 | 0.7 units on a scale | Standard Deviation 7.63 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitations Due to Physical Health Problems Domain | Baseline | 36.8 units on a scale | Standard Deviation 9.85 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitations Due to Physical Health Problems Domain | Change at Week 12 | 1.5 units on a scale | Standard Deviation 7.08 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Role Limitations Due to Physical Health Problems Domain | Change at Week 24 | 2.6 units on a scale | Standard Deviation 7.87 |
Comparison: Baseline to Week 1295% CI: [-3.92, 1.2]
Comparison: Baseline to Week 1295% CI: [-0.38, 4.35]
Comparison: Baseline to Week 12p-value: 0.0244ANCOVA
Secondary
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Social Functioning Domain
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Social Functioning score at Week x minus score at baseline.
Time frame: Baseline, Weeks 12, 24 or ET
Population: ITT; N=number of participants analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Social Functioning Domain | Baseline | 41.8 units on a scale | Standard Deviation 11.15 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Social Functioning Domain | Change at Week 12 | 0.4 units on a scale | Standard Deviation 9.72 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Social Functioning Domain | Change at Week 24 | 0.9 units on a scale | Standard Deviation 10.56 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Social Functioning Domain | Baseline | 41.5 units on a scale | Standard Deviation 10.19 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Social Functioning Domain | Change at Week 12 | 2.5 units on a scale | Standard Deviation 8.48 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Social Functioning Domain | Change at Week 24 | 0.7 units on a scale | Standard Deviation 9.61 |
Comparison: Baseline to Week 1295% CI: [-2.33, 3.23]
Comparison: Baseline to Week 1295% CI: [0.14, 5.32]
Comparison: Baseline to Week 12p-value: 0.1582ANCOVA
Secondary
Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Vitality Domain
SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change from baseline = Vitality score at Week x minus score at baseline.
Time frame: Baseline, Weeks 12, 24 or ET
Population: ITT; N=number of participants analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Vitality Domain | Baseline | 46.6 units on a scale | Standard Deviation 9.23 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Vitality Domain | Change at Week 12 | -0.7 units on a scale | Standard Deviation 8.22 |
| Sitaxsentan and Placebo | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Vitality Domain | Change at Week 24 | 1.4 units on a scale | Standard Deviation 7.84 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Vitality Domain | Baseline | 45.7 units on a scale | Standard Deviation 10.47 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Vitality Domain | Change at Week 12 | 3.2 units on a scale | Standard Deviation 8.74 |
| Sitaxsentan and Sildenafil | Change in 36-Item Short-Form Health Survey (SF-36) From Baseline at Weeks 12, 24 and 48 - Vitality Domain | Change at Week 24 | 2.9 units on a scale | Standard Deviation 9.8 |
Comparison: Baseline to Week 1295% CI: [-2.1, 2.97]
Comparison: Baseline to Week 1295% CI: [1.74, 6.45]
Comparison: Baseline to Week 12p-value: 0.0136ANCOVA