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

Pulmonary Arterial Hypertension Clinical Trial

— EPITOME-2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01431716
• Other study ID #: AC-066A301
• Status: Completed
• Phase: Phase 3
• First received: September 7, 2011
• Last updated: January 2, 2015
• Start date: March 2011
• Est. completion date: July 2012

Study information

• Verified date: January 2015
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsCanada: Ethics Review CommitteeCanada: Health CanadaFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)France: Committee for the Protection of PersonnesItaly: Ethics CommitteeNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Spain: Agencia Española de Medicamentos y Productos SanitariosSpain: Comité Ético de Investigación Clínica
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: July 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypertension
• Pulmonary Arterial Hypertension

Intervention

Drug:
• EFI/ACT-385781A

Locations

Country	Name	City	State
Belgium	UZ Gasthuisberg	Leuven
Canada	Sir Mortimer B Davis Jewish General Hospital	Montreal	Quebec
Canada	University Health Network, Toronto TGH - 10 EN - 220	Toronto	Ontario
France	Centre Hospitalier Universitaire	Caen
France	Hôpital Antoine Béclère	Clamart Cedex
Italy	Orsola Malpighi	Bologna
Netherlands	VU Medisch Centrum (VUMC)	Amsterdam
Spain	Hospital Vall d'Hebron	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

Belgium,  Canada,  France,  Italy,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Other	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	No
Other	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	No
Other	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	No
Other	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	No
Other	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	No
Other	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	No
Other	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	Yes
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No
Primary	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	No