The Effect of Tracleer® on Male Fertility

TRACLEER® (Bosentan) Pulmonary Arterial Hypertension A Multicenter, Open-label, Single-arm Safety Study to Investigate the Effects of Chronic TRACLEER® Treatment on Testicular Function in Male Patients With Pulmonary Arterial Hypertension

The objective of the study is to evaluate the effects of chronic TRACLEER® treatment on testicular function via semen analysis in male patients with primary pulmonary arterial hypertension (PAH).

Inclusion Criteria:

• Male patients age 18-65 years.
• Bosentan-naïve.
• PPH, WHO functional class III/IV, in need of TRACLEER
• Patients pulmonary arterial hypertension (PAH) secondary to congenital heart disease.
• Written informed consent.

Exclusion Criteria:

• Female
• Patients with PAH secondary to connective tissue vascular diseases or HIV.
• Patients who have undergone a vasectomy.
• Patients with an average baseline sperm concentration < 15 x 10[6]/mL, or any sample with a sperm concentration <= 7.5 x 10[6]/mL.
• Patients with an average baseline sperm motility <20% or normal sperm morphology <5%.
• Body weight < 50 kg.
• Hypotension, defined as systolic blood pressure less than 85 mm Hg.
• AST and/or ALT plasma levels greater than 3 times ULN.
• Hypersensitivity to bosentan or any of the components of the formulation.
• Treatment with glyburide, cyclosporine A or tacrolimus at inclusion or planned during the study.
• Treatment with hormone suppressive agents, including androgens, estrogens, anabolic steroids or glucocorticoids within the past 6 months or planned during the study.
• Current treatment less than 3 months prior to inclusion or planned treatment with prostacyclin or prostacyclin analogues (e.g., Flolanâ or Remodulin).
• Patients who received an investigational drug in the month preceding the study start or who are due to be treated with another investigational drug during the study period.
• Known drug or alcohol dependence or any other factors that will interfere with conduct of the study.
• Any illness other than PPH that will reduce life expectancy to less than 6 months.
• Active cancer.
• Prior treatment with an anti-neoplastic agent or ionizing radiation.
• Hot tub/Jacuzzi use.
• Uncontrolled diseases including diabetes, liver or kidney disease.
• Patients receiving spironolactone (aldactone) less than 3 months prior to inclusion or dose >25 mg/day at baseline or anytime during the study.