E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pulmonary Arterial Hypertension |
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E.1.1.1 | Medical condition in easily understood language |
Pulmonary Arterial Hypertension is a condition in which the pressure in the blood vessels going to the lungs (the pulmonary arteries) is higher than normal |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064911 |
E.1.2 | Term | Pulmonary arterial hypertension |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To evaluate the change in cardiac hemodynamics from baseline to 3-month following switch from Flolan® to EFI in patients with pulmonary arterial hypertension (PAH).
• To evaluate the safety and tolerability of switching from Flolan® to EFI in patients with PAH.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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 of EFI 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 enrollment
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
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E.5 End points |
E.5.1 | 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)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
- Weekly phone visit : Weeks 1, 2, and 3
- Inpatient Visit : Week 4
- By-weekly phone visit : Weeks 6, 8, and 10
Safety follow up:
- 24 hours post-EOT phone call
- 30 days post-EOT phone call
End of study:
- 24 hours post-EOT phone call for patients who participate in the extension study AC-066A302
- 30 days post-EOT phone call for patients not participating in the extension study AC-066A302 |
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E.5.2 | Secondary end point(s) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability, explaratory study phase 3b |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
France |
Italy |
Netherlands |
Spain |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last Patient Last End of Treatment Visit |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |