BREATHE 5-OL: Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology

Study Overview
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Brief Summary
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This 6-month open label study will evaluate the long term safety of bosentan (via oxygen saturation) and efficacy (exercise capacity) in patients who have completed the BREATHE-5 study (PAH related to Eisenmenger physiology). Treatment duration is 6 months.

Detailed Description
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This is a multicenter, open-label, single -arm study with bosentan, initial dose of 62.5 mg b.i.d., with a target dose of 125 mg b.i.d. All patients will be assessed for eligibility during the baseline visit (same as Week 16, end of study BREATHE-5 visit), and will have the option to enter into the open-label extension study at a starting dose of 62.5 mg b.i.d., for safety reasons. Visit 2 is required as a safety visit to assess oxygen saturation (SpO2) after 1 week of bosentan treatment. Patients will return for Visit 4 after 4 weeks of treatment, and the dose will be up-titrated to 125 mg b.i.d. or maintained at 62.5 mg b.i.d. at the judgement of the investigator. Data will be collected for a total of 24 weeks or until the sponsor decides to stop the study. If the results from Study AC-052-403 or AC-052-405 demonstrate significant safety issues, this extension study may be terminated at the sponsor's request.

Official Title
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A Multi-Center, Open-Label Extension Study to Protocol AC-052-405 to Evaluate the Safety and Efficacy of Tracleer (Bosentan) in Patients With Pulmonary Arterial Hypertension Related to Eisenmenger Physiology

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Drug: Tracleer®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients stable with PAH upon completion of the BREATHE-5 randomized, double-blind, placebo- controlled 16-week study. For female patients, only non-pregnant women who are surgically sterile, postmenopausal or have documented infertility (over 50 years of age and amenorrheic for at least 1 year), or those of childbearing potential using one of the following methods of contraception: Barrier-type devices (e.g., condom, diaphragm) used ONLY in combination with a spermicide. A double-barrier method is recommended; intrauterine devices (IUDs); oral or implanted contraceptives, if used in combination with a barrier method. Patients providing written informed consent. Exclusion Criteria: Patients who withdrew prematurely from BREATHE-5, AC-052-405. Patients who are pregnant or nursing. Patients who are receiving epoprostenol or prostacyclin analogues, or are expected to receive any of these drugs during the study. Patients with AST and/or ALT values greater than 3 times the upper limit of normal. Patients with hemoglobin or hematocrit that is more than 30% below the normal range (patients with secondary polycythemia are permitted in the study). Patients with systolic blood pressure < 85 mm Hg. Patients taking phosphodiesterase inhibitors, other endothelin receptor antagonists or are receiving another investigational product. Patients active on organ transplant list. Patients who are receiving or expected to receive glyburide, cyclosporin A or tacrolimus. Patients not able to comply with the protocol or adhere to therapy.

Ages Eligible for Study
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Minimum Age: 12 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: Tracleer<br>The starting dose for all patients will be 62.5 mg b.i.d. At the Week 4 visit, patients who were started on 62.5 mg b.i.d. will be uptitrated to 125 mg b.i.d. if the 62.5 mg b.i.d. dose was well-tolerated. | Drug: Tracleer®<br>* Patients will receive up to 125 mg b.i.d. of Tracleer.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 6-minute Walk Distance |  | from baseline to week 24 | 
| Change in Borg Dyspnea Index | Borg scale a numerical scale for assessing dyspnea, from 0 representing no dyspnea to 10 as maximal dyspnea. | from baseline to week 24 | 
| Number of Participants With a Change in WHO Functional Class | Number of participants with a change in WHO functional class from baseline to week 24. A change from a higher to a lower functional class (i.e. III to II, III to I or II to I) is considered as an improvement. | from baseline to week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bosentan, PAH related to Eisenmenger physiology, Tracleer