The Effect of Tracleer® on Male Fertility

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Hypertension, Pulmonary

Intervention / Treatment
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* Drug: bosentan


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

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: 1<br>Oral bosentan tablets | Drug: bosentan<br>* Oral bosentan tablets 62.5 mg twice daly for 4 weeks, then 125 mg twice daily for 20 weeks.<br>* Other names: Tracleer (R);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with a mean decrease in sperm concentration to 7.5 x 10[6]/mL or below, without a single sperm concentration ≥ 20 x 10[6]/mL, at 3 or 6 months. This proportion is considered of clinical relevance if greater than 30%. |  | From baseline to end of study. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Semen volume, sperm motility and sperm morphology change |  | From baseline to 3 & 6 months |