Study Providing Monotherapy (Sitaxsentan) And Combination Therapy (Sitaxsentan+Sildenafil) To Subjects With Pulmonary Arterial Hypertension (PAH) To Assess Long-Term Safety

Study Overview
=================
Brief Summary
-----------------
As sitaxsentan is the agent most highly selective for ETA (Endothelin Type A (receptor)), and does not significantly impact sildenafil pharmacokinetics the combination of most promise for pulmonary arterial hypertension (PAH) therapy is these two oral drugs administered in combination.

Official Title
-----------------
A Phase 3, Multi-Center, Open Label Study To Evaluate The Long-Term Safety Of Monotherapy Sitaxsentan Sodium And Combination Therapy With Sitaxsentan Sodium And Sildenafil Citrate In Subjects With Pulmonary Arterial Hypertension

Conditions
-----------------
Pulmonary Arterial Hypertension, Pulmonary Hypertension

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Previously enrolled in B1321001 for at least 4 weeks. Previously enrolled in B1321003, discontinued from the study. Completed the B1321003 study as planned. Exclusion Criteria: Treated with an investigational drug (other than sitaxsentan or sildenafil in either B1321001 or B1321003) 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
-----------------
Minimum Age: 16 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitaxsentan<br>Monotherapy arm | Drug: Sitaxsentan<br>* Sitaxsentan = 100 mg tablet administered orally, once daily<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?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival is the duration from first dose to death. For participants who are lost to follow-up, survival was censored at the last date of follow-up. | Baseline and every 12 weeks up to Week 18 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 6 Minute Walk Distance at Weeks 12 and 24 | The walk distance was the total distance walked during the 6-minute test. Change is distance walked at week x minus distance walked at baseline. | Baseline, Weeks 12 up to Early Termination (ET) (up to Week 18) | 
| Number of Participants in Each World Health Organization (WHO) Functional Class of Pulmonary Arterial Hypertension (PAH) | The WHO functional classes of PAH range from Class 1 (no limitation in physical activity) to Class IV (can not perform a physical activity without any symptoms). | Baseline, Week 12 and ET (up to Week 18) | 

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