Study Looking at Combination Therapy (Sitaxsentan+Sildenafil) Vs. Monotherapy (Sitaxsentan Alone) SR-PAAS -Sitaxsentan Efficacy And Safety Trial With A Randomized Prospective Assessment Of Adding Sildenafil

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 3, Multi-Center, Randomized, Double-Blind, Efficacy And Safety Study Of Monotherapy Sitaxsentan Sodium Versus Combination Therapy With Sitaxsentan Sodium And Sildenafil Citrate In Subjects With Pulmonary Arterial Hypertension Who Have Completed Study B1321001 (NCT00795639)

Conditions
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Pulmonary Arterial Hypertension, Pulmonary Hypertension

Intervention / Treatment
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* Drug: Sitaxsentan
* Drug: Sitaxsentan and Sildenafil


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitaxsentan and Placebo<br>Monotherapy arm | Drug: Sitaxsentan<br>* Sitaxsentan = 100 mg tablet administered orally, once daily Sildenafil placebo = 1 tablet administered orally, three times a day<br>|
| Experimental: Sitaxsentan and Sildenafil<br>Combination treatment | Drug: Sitaxsentan and Sildenafil<br>* Sitaxsentan = 100 mg tablet administered orally, once daily plus Sildenafil = 20 mg tablet administered orally, three times a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Weeks 12, 24 or Early Termination (ET) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline to Weeks 12 and 24 | 
| 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. | Baseline, Weeks 12, 24 or ET | 
| 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. | Baseline, Weeks 12, 24 and ET | 
| 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. | Baseline, Weeks 12, 24 or ET | 
| 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. | Baseline, Weeks 12, 24 or ET | 
| 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. | Baseline, Weeks 12, 24 or ET | 
| 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. | Baseline, Weeks 12, 24 or ET | 
| 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. | Baseline, Weeks 12, 24 or ET | 
| 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. | Baseline, Weeks 12, 24 or ET | 
| 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. | Baseline, Weeks 12, 24 or ET | 
| 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. | Baseline, Weeks 12, 24 or ET | 
| 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. | Baseline, Weeks 12, 24 or ET | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endothelin receptor antagonist (ETRA), Sitaxsentan