Epoprostenol for Injection (EFI/ACT-385781A) - Pulmonary Arterial Hypertension

A Multicenter, Single-arm, Open-label, Phase 3b Study to Assess the Effects of Switching From Flolan® to EFI/ACT-385781A in Patients With Pulmonary Arterial Hypertension

This study is investigating the effect of switching from Flolan® to Epoprostenol for Injection (EFI/ACT-385781A) in pulmonary arterial hypertension patients currently treated with Flolan®. For this purpose patients being treated for at least 12 months with Flolan® will be switched from Flolan® to EFI/ACT-385781A and followed-up for 90 days. During these 90 days safety and tolerability of EFI/ACT-385781A will closely be monitored in all treated patients. This 90 follow-up will provide clinical evidence on the safety, tolerability, efficacy and treatment satisfaction of switching from Flolan® to EFI/ACT-385781A in patients with pulmonary arterial hypertension.

Inclusion Criteria:

1. Male or female aged 18 years and above
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 or Drugs and toxins
3. Patients treated with Flolan® for at least 12 months and on a stable dose for at least 3 months prior to enrollment
4. Patients who are currently treated with concomitant PAH therapy listed below must have been treated for at least 90 days and on a stable dose for 30 days prior to enrollment: Bosentan, Ambrisentan, Sitaxsentan, Sildenafil, Tadalafil
5. Women of childbearing potential must use a reliable method of contraception
6. Signed informed consent prior to initiation of any study mandated procedure

Exclusion Criteria:

1. Patients with respiratory and/or cardiovascular distress in need of emergency care

2. Known or suspicion of pulmonary veno-occlusive disease (PVOD)

3. Current use of IV inotropic agents

4. Current use of any prostacyclin or prostacyclin analog other than Flolan®

5. Tachycardia with heart rate > 120 beats/min at rest

6. PAH related to any condition other than those specified in the inclusion criteria

7. Known hypersensitivity to the formulations EFI/ACT-385781A or any of its excipients, and Flolan® or any of its excipients

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 disorders

12. Central venous line infection within 90 days prior to screening and/or a history of recurring line infections

13. Women who are pregnant or breast-feeding

14. Participation in another clinical trial, except observational, 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