Epoprostenol for Injection (EFI/ACT-385781A) - Pulmonary Arterial Hypertension (EPITOME-2)

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: EFI/ACT-385781A

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Gasthuisberg
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network, Toronto TGH - 10 EN - 220
  • Quebec
    • Montreal, Quebec, Canada, H3T 1 E2
      • Sir Mortimer B Davis Jewish General Hospital
• France
  • Caen, France, 14033
    • Centre Hospitalier Universitaire
  • Clamart Cedex, France, 92141
    • Hôpital Antoine Béclère
• Italy
  • Bologna, Italy, 40138
    • Orsola Malpighi
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU Medisch Centrum (VUMC)
• Spain
  • Barcelona, Spain, 8035
    • Hospital Vall d'Hebron

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EFI/ACT-385781A; EFI/ACT-385781 administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump	Drug: EFI/ACT-385781A; Other Names: ACT-385781A; Epoprostenol for injection (EFI)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Pulmonary Vascular Resistance From Baseline to End of Treatment (EOT).	Right heart catheterization was performed for cardiac hemodynamic assessment at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT.	Approximately 3 months
Change in Total Pulmonary Resistance From Baseline to End of Treatment (EOT).	Right heart catheterization was performed for cardiac hemodynamic assessment at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT.	Approximately 3 months
Change in Mean Pulmonary Arterial Pressure From Baseline to End of Treatment (EOT).	Right heart catheterization was performed for cardiac hemodynamic assessment at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT.	Approximately 3 months
Change in Mean Right Atrial Pressure From Baseline to End of Treatment (EOT).	Right heart catheterization was performed for cardiac hemodynamic assessment at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT.	Approximately 3 months
Change in Pulmonary Capillary Wedge Pressure From Baseline to End of Treatment (EOT).	Right heart catheterization was performed for cardiac hemodynamic assessment at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT.	Approximately 3 months
Change in Mean Cardiac Index From Baseline to End of Treatment (EOT).	Right heart catheterization was performed for cardiac hemodynamic assessment at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT.	Approximately 3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 6-minute Walk Distance (6MWD) From Baseline to EOT.	The 6MWD was assessed at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT. The 6-minute walk test is a non-encouraged test that measures the distance walked for the duration of 6 min.	Approximately 3 months
Change in Borg Dyspnea Score From Baseline to EOT.	The Borg dyspnea score was assessed at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT. The Borg scale is a category-ratio scale, commonly used to evaluate the effects of exercise on dyspnea. The original and modified scales have ratio properties ranging from 0 = nothing at all to 10 = very, very severe, with descriptors from 0 to 10. Descriptors have been modified by others so that 10 has been labelled "extremely severe," or "the worst possible dyspnea imaginable."	Approximately 3 months
Number of Participants With Improved, No Change, or Worsening of New York Heart Association Functional Class (NYHA FC) From Baseline to EOT.	NYHA FC was assessed at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT. Disease severity was assessed by NYHA classification of pulmonary arterial hypertension criteria: Class I: no limitation of physical activity (PA). Ordinary PA: no undue dyspnea/fatigue, chest pain, near syncope. Class II: slight limitation of PA. Comfortable at rest. Ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class III: marked limitation of PA. Comfortable at rest. Less than ordinary PA: undue dyspnea/fatigue, chest pain, near syncope. Class IV: inability to carry out PA without symptoms. Right heart failure. Dyspnea/fatigue may even have been present at rest. Discomfort increased by any PA.	Approximately 3 months
Change in N-terminal Pro-B-type Natriuretic Peptide (NT proBNP) From Baseline to EOT.	Blood sampling for NT proBNP was performed at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT.	Approximately 3 months
Change in Effectiveness Score of the Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to EOT.	Patients were required to complete the TSQM-9 questionnaire at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT. The TSQM-9 is a validated instrument to assess patients' satisfaction with medication, including a three question effectiveness scale. The TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain.	Approximately 3 months
Change in Convenience Score of the Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to EOT.	Patients were required to complete the TSQM-9 questionnaire at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT. The TSQM-9 is a validated instrument to assess patients' satisfaction with medication, including a three question convenience scale. The TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain.	Approximately 3 months
Change in Global Satisfaction Score of the Abbreviated Treatment Satisfaction Questionnaire for Medication (TSQM-9) From Baseline to EOT.	Patients were required to complete the TSQM-9 questionnaire at Screening or Day 1, prior to switch from Flolan® to EFI/ACT-385781A and at EOT. The TSQM-9 is a validated instrument to assess patients' satisfaction with medication, including a three question global satisfaction scale. The TSQM-9 domain scores range from 0 to 100 with higher scores representing higher satisfaction on that domain.	Approximately 3 months
Number of Participants With Adverse Events Leading to Discontinuation of Study Drug From Baseline to EOT.	Adverse events that led to discontinuation of study drug from the start of study treatment until the end of study treatment were recorded.	Approximately 3 months

Collaborators and Investigators

• Sponsor: Actelion

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: September 7, 2011
• First Submitted That Met QC Criteria: September 9, 2011
• First Posted (Estimate): September 12, 2011

Study Record Updates

• Last Update Posted (Estimate): January 13, 2015
• Last Update Submitted That Met QC Criteria: January 2, 2015
• Last Verified: January 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Antihypertensive Agents; Platelet Aggregation Inhibitors; Epoprostenol
• Other Study ID Numbers: AC-066A301