Bosentan in Children With Pulmonary Arterial Hypertension

Inclusion Criteria:

- Signed informed consent by the parents or the legal representatives.

- Males or females >= 2 and < 12 years of age.

- Idiopathic PAH or familial PAH diagnosed by right heart catheterization (Clinical
classification of pulmonary hypertension, Venice 2003).

- World Health Organization (WHO) functional class II or III.

- Oxygen saturation (SpO2) >= 88% (at rest, on room air).

- PAH treatment-naïve patients or patients already treated with either:

- Bosentan monotherapy

- Intravenous epoprostenol monotherapy

- Intravenous or inhaled iloprost monotherapy

- Combination of bosentan and intravenous epoprostenol

- Combination of bosentan and intravenous or inhaled iloprost.

- All patients should start the study drug (bosentan pediatric formulation) at 2 mg/kg
twice daily (b.i.d.), whether or not they were previously treated with bosentan.

- PAH therapy stable for at least 3 months prior to Screening.

- Stable treatment with calcium channel blockers, if any, for at least 3 months prior
to Screening.

- Patient's PAH condition stable for at least 3 months prior to Screening.

Exclusion Criteria:

- PAH associated with conditions other than idiopathic or familial PAH.

- Non-stable patients, e.g., history (in the last 3 months prior to Screening) of
recurrent syncope, or signs and symptoms of non-compensated right heart failure.

- Need or plan to wean patients from intravenous epoprostenol, or intravenous, or
inhaled iloprost.

- Body weight < 4 kg.

- Systolic blood pressure < 80%, the lower limit of normal range, according to age and
gender.

- AST and/or ALT values > 3 times the upper limit of normal ranges.

- Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.

- Hemoglobin and/or hematocrit levels < 75% of the lower limit of normal ranges.

- Pregnancy.

- Known intolerance or hypersensitivity to bosentan or any of the excipients.