Inclusion Criteria

Patients must:

• Be between 18 years and 75 years of age.
• If female, be physiologically incapable of childbearing or practicing an acceptable method of birth control.
• Have a current confirmed diagnosis of WHO Functional Class II or III pulmonary arterial hypertension (either PPH or PAH associated with the scleroderma spectrum of diseases).
• Have been clinically stable with regard to signs and symptoms of PAH for at least the last 30 days.
• Have a baseline six-minute walk distance of at least 250 meters.
• Have been receiving Flolan therapy for at least 6 months, and have documented clinical benefit from Flolan therapy on an exercise assessment.
• Be receiving Flolan at a dose of at least 15 ng/kg/min, but not more than 75 ng/kg/min, and have maintained the current dose of Flolan unchanged for at least 30 days at screening.
• Unless contraindicated, be able to receive one of the following anticoagulants: warfarin to achieve an INR between 2.0 and 3.0 or heparin to produce an aPTT between 1.3 to 1.5 times control, unless higher levels are clinically indicated.
• Be mentally and physically capable of learning to administer study drug using an subcutaneous infusion pump.

Exclusion Criteria

Patients must not:

• Be a nursing or pregnant woman (women of childbearing potential must have a negative serum pregnancy test).
• Have had a new type of chronic therapy (including but not limited to oxygen, a different category of vasodilator, a diuretic, digoxin) for pulmonary hypertension added within the last month.
• Have any pulmonary hypertension medication except for anticoagulants discontinued within the week prior to study entry.
• Have ever received Remodulin or any other prostaglandin/prostacyclin analog other than Flolan or Beraprost; or have received Bosentan or any other endothelin receptor antagonist within the past 30 days.

• Have evidence of significant parenchymal lung disease as evidenced by pulmonary function tests within the last six months as follows (any one of the following):

  1. Total Lung Capacity < 60% (predicted), or
  2. If Total Lung Capacity is between 60% and 70% (predicted), a High Resolution CT scan must be performed to document diffuse interstitial fibrosis or alveolitis, or

  3. FEV/FVC ratio < 50%, or

     • All Scleroderma patients must have Pulmonary Function Test performed within six weeks prior to study entry.
• Be positive for HIV.
• Have Portal Hypertension.
• Have a history of uncontrolled Sleep Apnea within the past three months.

• Have a history of left-sided heart disease including:

  1. Aortic or mitral valve disease or,
  2. Pericardial constriction or,
  3. Restrictive or congestive cardiomyopathy.

• Have evidence of current left-sided heart disease as defined by:

  1. PCWPm or left ventricular end diastolic pressure > 15 mmHg or
  2. LVEF < 40% by MUGA or Angiography or echocardiography or
  3. LV Shortening Fraction < 22% by echocardiography or
  4. Symptomatic coronary disease (demonstrable ischemia).
• Have any other disease that is associated with pulmonary hypertension (e.g. congenital systemic to pulmonary shunt, sickle cell anemia, schistosomiasis).
• Have a musculoskeletal disorder (e.g. arthritis, artificial leg, etc.) or any other disease, which is thought to limit ambulation, or be connected to a machine, which is not portable.
• Have uncontrolled systemic hypertension as evidenced by systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg.
• Have used prescription appetite suppressants within 3 months of study entry.
• Have chronic renal insufficiency as defined by creatinine greater than 3.5 mg/dL or the requirement for dialysis.
• Be receiving an investigational drug, have in place an investigational device, or have participated in an investigational drug study within the past 30 days.
• Have had an atrial septostomy.
• Have anemia (hemoglobin <10 g/dL), active infection or any other ongoing condition that would interfere with the interpretation of study assessments.
• Have any serious or life-threatening disease other than conditions associated with PAH (e.g. malignancy requiring aggressive chemotherapy, renal dialysis, etc.).
• Have unstable psychiatric status or be mentally incapable of understanding the objectives, nature or consequences of the trial, or any condition which in the investigator’s opinion would constitute an unacceptable risk to the patient’s safety.