Safety, Tolerability, Pharmacokinetics and Efficacy of Two Different Rates of Subcutanous Remodulin® Dose Titration in Pulmonary Arterial Hypertension

Inclusion Criteria: A subject is eligible for inclusion in this study if all of the following criteria apply: 1. The subject voluntarily gives written informed consent to participate in the study. 2. The subject is at least 18 years of age at screening. 3. The subject weighs a minimum of 40 kg with a body mass index less than 40 kg/m2 at screening. 4. The subject has a diagnosis of idiopathic or heritable PAH, PAH associated with repaired congenital systemic-to-pulmonary shunts (at least one year since repair with respect to the date of providing informed consent), or PAH associated with connective tissue diseases. 5. The subject must have a baseline 6MWD between 150 and 550 meters, inclusive, in the absence of a concurrent injury, illness (other than PAH or a PAH related condition), or other confounding factor that would prevent the accurate assessment of the subject's exercise capacity. 6. The subject is either treatment naïve or is receiving a PDE-5 inhibitor and/or an ERA for at least 60 days prior to screening and on a stable dose for at least 30 days prior to screening and is willing to remain on a PDE-5 inhibitor and/or an ERA at the same dose for the duration of the 16-week treatment phase. 7. The subject must be optimally treated with conventional pulmonary hypertension therapy (e.g., oral vasodilators, oxygen, digoxin, etc.) with no additions, discontinuations, or dose changes for at least 14 days prior to screening (excluding diuretics and anticoagulant dose adjustments). 8. The subject has undergone right heart catheterization during the screening period (or within 3 years before screening) and been documented to have a mean pulmonary artery pressure (PAPm) of greater than or equal to 25 mmHg, a pulmonary arterial wedge pressure (PAWP) of less than or equal to 15 mmHg, and pulmonary vascular resistance (PVR) of more than 3 Wood units. 9. The subject has undergone echocardiography within 7 days prior to randomisation with evidence of clinically normal left systolic and diastolic ventricular function, absence of any clinically significant left sided heart disease (e.g., mitral valve stenosis) and absence of unrepaired congenital heart disease. Subjects with clinically insignificant left ventricular diastolic dysfunction due to the effects of right ventricular overload (i.e., right ventricular hypertrophy and/or dilatation) will not be excluded. 10. The subject has a previous ventilation perfusion lung scan and/or high resolution computerized tomography scan of the chest and/or pulmonary angiography that are consistent with the diagnosis of PAH (e.g., low probability of pulmonary embolism; absence of major perfusion defects). 11. The subject has pulmonary function tests done within 9 months prior to or during the screening period with the following: 1. Total lung capacity (TLC) is at least 60% (of predicted value) 2. Forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio is at least 50% 12. Sexually active women of childbearing potential must practice true abstinence from intercourse when it is in line with their preferred and usual lifestyle, or use two different forms of highly effective contraception. Medically acceptable forms of effective contraception include: (1) approved hormonal contraceptive (such as birth control pills), (2) barrier methods (such as a condom or diaphragm) used with a spermicide, (3) an intrauterine device (IUD), or (4) partner vasectomy. For women of childbearing potential, a negative serum pregnancy test is required at screening and a negative hCG urine pregnancy test is required at baseline visit. Women of child bearing potential include any females who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or are not postmenopausal (defined as amenorrhea for at least 12 consecutive months). Males participating in the study must use a condom during the length of the study, and for at least 48 hours after discontinuing study medication. 13. In the opinion of the Principal Investigator, the subject is able to communicate effectively with study personnel, is considered reliable, willing and likely to be cooperative with protocol requirements, including attending all study visits, and is mentally and physically capable of learning to administer Remodulin by continuous SC infusion using a micro infusion pump. Exclusion Criteria: A subject is not eligible for inclusion in this study if any of the following criteria apply: 1. The subject is pregnant or lactating. 2. The subject has received epoprostenol, treprostinil, iloprost or beraprost within 90 days prior to screening (except if used during acute vasoreactivity testing). 3. The subject has had previous intolerance or lack of efficacy to prostacyclin or a prostacyclin analogue that resulted in discontinuation or inability to titrate that therapy effectively. 4. The subject has any disease associated with PH other than idiopathic or heritable PAH, or PAH associated with repaired (for at least one year) congenital systemic-to-pulmonary shunts or connective tissue diseases or has had an atrial septostomy. 5. The subject is in WHO functional class IV. 6. The subject has a current diagnosis of uncontrolled sleep apnea as defined by their physician. 7. The subject has liver function tests (AST or ALT) greater than three times the upper limit of the laboratory reference range. 8. The subject has a history of active gastro-intestinal ulcer, intracranial hemorrhage, injury or other cause of clinically significant bleeding episode within 6 months before screening, or any other disease / condition that would either jeopardize the safety of the subject and / or interfere with the interpretation of study assessments in the opinion of the Investigator. 9. The subject has a history of ischemic heart disease including previous myocardial infarction or symptomatic coronary artery disease within 6 months before screening, or history of left sided myocardial disease as evidenced by a PAWP (or left ventricular end-diastolic pressure) greater than 15 mmHg or left ventricular ejection fraction (LVEF) less than 40%. 10. The subject has uncontrolled systemic hypertension as evidenced by systolic blood pressure greater than 160 mmHg or diastolic blood pressure greater than 100 mmHg. 11. The subject has systemic hypotension as evidenced by systolic blood pressure less than 85 mmHg 12. The subject has a musculoskeletal disorder (e.g., arthritis affecting the lower limbs, recent hip or knee joint replacement, artificial leg) or any other disease that is likely to limit ambulation, or is connected to a machine that is not portable. 13. The subject has an unstable psychiatric condition or is mentally incapable of understanding the objectives, nature, or consequences of the trial, or has any condition which in the Investigator's opinion would constitute an unacceptable risk to the subject's safety. 14. The subject is receiving an investigational drug, has an investigational device in place or has participated in an investigational drug or device study within 30 days prior to screening.