Safety and Efficacy Study of Sitaxentan Sodium (Thelin™) in Patients With Pulmonary Arterial Hypertension

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Safety and Efficacy Study of Sitaxsentan Sodium (Thelin™) Treatment With an Open-Label Bosentan Arm in Patients With Pulmonary Arterial Hypertension (PAH)

The purpose of this study is to evaluate the safety and efficacy of Thelin™ (sitaxsentan sodium) compared to placebo (sugar pill) in the treatment of patients with pulmonary arterial hypertension (PAH).

The purpose of this study is to evaluate the safety and efficacy of Thelin™ (sitaxsentan sodium) as compared to placebo in the treatment of patients with PAH. A cohort of patients will be randomized to usual treatment with Tracleer® (bosentan) for observational comparisons of safety and efficacy.

Inclusion Criteria:

• Have a current diagnosis of symptomatic PAH classified by one of the following:

  1. primary pulmonary hypertension (PPH) - also known as idiopathic pulmonary arterial hypertension (IPAH);

  2. PAH associated with connective tissue diseases;

  3. PAH associated with one of the following congenital heart defects:

     1. repaired ASD, VSD or PDA greater than one year post-operative
     2. un-repaired secundum ASD (with resting oxygen saturation greater than 88 percent in room air measured by oximeter)

• World Health Organization (WHO) functional class II, III, IV

• Greater than 12 and less than 75 years of age

• Women of childbearing potential must be using two forms of medically acceptable contraception (at least one barrier method)

• Have a cardiac catheterization within 6 months before study entry that shows the following values:

  1. mean pulmonary artery pressure (PAPm) greater than 25 mmHg (at rest),
  2. pulmonary capillary wedge pressure (PCWP) or left ventricular-end diastolic pressure less than 15 mmHg, and
  3. pulmonary vascular resistance (PVR) greater than 3 mmHg/L/min.

Exclusion Criteria:

• Portal hypertension or chronic liver disease
• ALT or AST levels greater than 1.5 times the upper limit of normal at the Screening Visit
• Contraindication to treatment with an endothelin receptor antagonist
• Recent history of abusing alcohol or illicit drugs
• Chronic renal insufficiency
• Pregnant or breastfeeding
• Atrial septostomy within 30 days before study entry
• Previous failure on bosentan because of safety concerns of the lack of clinical response