A 12 Week Safety And Efficacy Study Of Sitaxentan Sodium In Japanese Pulmonary Arterial Hypertension Patients

Study Overview
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Brief Summary
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The safety and efficacy at 100 mg once daily for oral dose of sitaxentan sodium were demonstrated in the STRIDE clinical trial program. Sitaxentan sodium was approved in the EU, Canada and Australia. In this study, the safety and efficacy after administrations of sitaxentan sodium at a dose of 100 mg alone or in combination with another medication will be investigated in Japanese PAH patients.

Official Title
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A Phase 3, Multi-Center, Open Label Study To Evaluate The Safety And Efficacy Of Sitaxentan Sodium In Japanese Subjects With Pulmonary Arterial Hypertension

Conditions
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Hypertension, Pulmonary

Intervention / Treatment
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* Drug: Sitaxentan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a current diagnosis of symptomatic PAH Has 6MWT distances from 150 to 450 meters and distance Exclusion Criteria: Previous exposure to an endothelin receptor antagonist Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure >160 mm Hg or sitting diastolic blood pressure >100 mm Hg at Screening. Has hypotension defined as systolic arterial pressure <90 mm Hg after sitting for 5 minutes at Screening.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitaxentan treatment<br> | Drug: Sitaxentan<br>* sitaxentan sodium 100 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Number of participants with any adverse events, severe adverse events, serious adverse events | 12 weeks | 
| Change From Baseline in 6-minute Walk Distance | Change from baseline in 6-minute walk distance is calculated as the value at Week 12 minus value at baseline. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in WHO Functional Class | The change from baseline in WHO functional class was classified into Improved, No change and Worsened. The change from baseline in WHO functional class at Week 12 was to be summarized with frequency count and percentage in each category based on imputed data for missing values at Week 12. | 12 weeks | 
| Number of Participants With Haemodynamics Parameters | The following haemodynamic measurements were assessed: right arterial pressure, pulmonary arterial systolic pressure, pulmonary arterial diastolic pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, left ventricular-end diastolic pressure, cardiac output, systemic arterial blood pressure (systolic, diastolic and mean), and heart rate. Change from baseline in haemodynamics parameters is calculated as the value at Week 12 minus value at baseline. | 12 weeks | 
| Change From Baseline in N-amino Terminal Fragment of the Prohormone Brain Natriuretic Peptide (NT-pro BNP) | Change from baseline in NT-pro BNP is calculated as the value at Week 12 minus value at baseline. | 12 weeks | 
| Clinical Worsening | Clinical worsening is defined as 1) Hospitalization for worsening pulmonary arterial hypertension, 2) On-study death, 3) Heart-lung or lung transplantation, 4) Atrial septostomy, 5) Addition of the chronic medications for the treatment of worsening pulmonary arterial hypertension, and 6) Initiation of oxygen. | 12 weeks | 
| Number of Participants With Pharmacokinetic (PK) Parameters at Steady State | The following PK parameters at the steady state were evaluated: maximum observed concentration during the dosing interval (Cmax), time for maximum observed concentration during the dosing interval (Tmax), area under the plasma concentration-time curve over dosing interval tau for multiple dose (AUCtau), terminal elimination half-life (t1/2), apparent clearance (CL/F) and apparent volume of distribution during the terminal elimination phase (Vz/F) at Week 12/Termination (as data permit), and concentration predose during multiple dosing (Ctrough) at Week 2, 4, 8 and 12/Termination. | pre-dose at Week 2, 4, 8, and pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours post-dose at Week 12 or study termination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sitaxentan sodium hypertension