Epoprostenol for Injection in Pulmonary Arterial Hypertension
Condition: Pulmonary Arterial Hypertension
MeSH terms: Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Hypertension
Intervention: ACT-385781A (Actelion Epoprostenol); Flolan®
Intervention description: per Prescribing Information; Per Prescribing Information
Intervention MeSH terms: Epoprostenol; Tezosentan
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Pulmonary Arterial Hypertension; PAH; EPITOME-1

Summary:

      This is a prospective, multi-center, open-label, randomized, Phase IV exploratory study
      comparing safety, tolerability, pharmacokinetics, and effectiveness of ACT-385781A and Flolan
      (epoprostenol sodium) in patients with pulmonary arterial hypertension who are naïve to
      injectable prostanoid treatment and in need of such treatment. Approximately 30 patients from
      8 U.S. clinical sites will be randomized to receive either ACT-385781A or Flolan (2:1
      respectively) for 28 days of treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female subjects aged 18-65 years

          2. Patients with the following types of pulmonary arterial hypertension (PAH) belonging
             to WHO Group I:

               -  Idiopathic (IPAH)

               -  Heritable (HPAH)

               -  Associated (APAH) with

                    -  Connective tissue diseases

                    -  Drugs and toxins

          3. Patients with PAH in modified NYHA functional class III or IV at the time of
             enrollment in need of injectable epoprostenol.

          4. Patients must be injectable prostanoid treatment-naïve and either

               -  newly diagnosed and not yet treated with specific PAH therapies or

               -  currently treated with existing background PAH therapy with one or more of the
                  following medications for 90 days prior to enrollment and on a stable dose for 30
                  days prior to enrollment:

                    -  Bosentan

                    -  Ambrisentan

                    -  Sildenafil

                    -  Tadalafil

          5. Women of childbearing potential must use a reliable method of contraception.

        Exclusion Criteria:

          1. Patients with respiratory and/or cardiovascular distress in need of emergency care
             including i.v. epoprostenol administration or any vasopressive i.v. drugs

          2. Known pulmonary veno-occlusive disease (PVOD)

          3. Current use of i.v. inotropic agents

          4. Tachycardia with heart rate > 120 beats/min

          5. Pulmonary arterial hypertension related to any condition other than those specified in
             the inclusion criteria

          6. Known hypersensitivity to the formulations of ACT-385781A or any of its excipients,
             and Flolan or any of its excipients

          7. Use of inhaled iloprost or treprostinil during the week prior to screening

          8. Cerebrovascular events (e.g., transient ischemic attack or stroke) within 6 months of
             screening

          9. History of myocardial infarction

         10. History of left-sided heart disease, including any of the following:

               -  hemodynamically significant aortic or mitral valve disease

               -  restrictive or congestive cardiomyopathy

               -  left ventricular ejection fraction < 40% by multigated radionucleotide
                  angiogram(MUGA),angiography, or echocardiography

               -  unstable angina pectoris

               -  life-threatening cardiac arrhythmias

         11. Chronic bleeding disorder

         12. Infection(s) within the past month that in the mind of the investigator would
             contraindicate the use of epoprostenol

         13. Pregnancy or breast-feeding

         14. Participation in another clinical trial, except observational (noninterventional), or
             receipt of an investigational product within 30 days prior to randomization

         15. Any known factor or disease that might interfere with treatment compliance, study
             conduct or interpretation of the results such as drug or alcohol dependence or
             psychiatric disease

         16. Known concomitant life-threatening disease other than PAH with a life expectancy < 12
             months