A Multicenter, Single-arm, Open-label, Phase 3b Study to Assess the Effects of Switching From Flolan® to ACT-385781A in Patients with Pulmonary Arterial Hypertension - EPITOME-2

• Register: EUCTR
• Last refreshed on: 18 October 2021
• Main ID: EUCTR2010-018322-40-FR
• Date of registration: 29/03/2010
• Prospective Registration: Yes
• Primary sponsor: ACTELION Pharmaceuticals Ltd
• Public title: A Multicenter, Single-arm, Open-label, Phase 3b Study to Assess the Effects of Switching From Flolan® to ACT-385781A in Patients with Pulmonary Arterial Hypertension - EPITOME-2
• Scientific title: A Multicenter, Single-arm, Open-label, Phase 3b Study to Assess the Effects of Switching From Flolan® to ACT-385781A in Patients with Pulmonary Arterial Hypertension - EPITOME-2
• Date of first enrolment: 20/05/2010
• Target sample size: 20
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-018322-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, France, Italy, Netherlands, Spain

Key inclusion & exclusion criteria

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
o Connective tissue diseases
o Drugs and toxins
3. Patients treated with Flolan® for at least 12 months and on a stable dose for at least 3 month 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 Epoprostenol-Actelion 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



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Pulmonary Arterial Hypertension
MedDRA version: 12.1 Level: LLT Classification code 10064911 Term: Pulmonary arterial hypertension

Intervention(s)

Trade Name: Epoprostenol-Actelion
Product Name: Epoprostenol-Actelion
Product Code: ACT-385781A
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: EPOPROSTENOL SODIUM
CAS Number: 61849-14-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.5-

Primary Outcome(s)

Main Objective: • To evaluate the change in cardiac hemodynamics from baseline to 3-month following switch from Flolan® to Epoprostenol-Actelion in patients with pulmonary arterial hypertension (PAH).
• To evaluate the safety and tolerability of switching from Flolan® to Epoprostenol-Actelion in patients with PAH.

Primary end point(s): Tolerability / Safety endpoints:
• Treatment-emergent adverse events (AEs) up to 24 hours post-EOT
• Change from baseline to EOT in vital signs [heart rate (HR) and blood pressure (BP)] and body weight
• AEs leading to premature discontinuation of study drug
• Treatment-emergent serious AEs (SAEs) up to 30 days post-EOT


Efficacy endpoint:
• Change from baseline to EOT in cardiac hemodynamics including:
o Pulmonary vascular resistance (PVR)
o Mean pulmonary arterial pressure (mPAP)
o Right atrial pressure (RAP)
o Pulmonary artery occlusion pressure (PAOP)
o Cardiac index (CI)

Secondary Objective:

Secondary ID(s)

AC-066A301

Ethics review

Status: Approved
Approval date: 20/05/2010
Contact:

Results

• Results available: Yes
• Date Posted: 17/06/2017
• Date Completed: 02/02/2012
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-018322-40/results