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

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.

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.