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    Summary
    EudraCT Number:2010-018322-40
    Sponsor's Protocol Code Number:AC-066A301
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-01-05
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2010-018322-40
    A.3Full title of the trial
    Uno studio multicentrico, a braccio singolo, in aperto, di fase 3b, per valutare gli effetti del passaggio da Flolan ad ACT 385781A nei pazienti con ipertensione arteriosa polmonare
    A multicenter, single-arm, open-label, Phase IIIb Study to Assess the Effects of Switching From Flolan to ACT-385781A in patients with Pulmonary Arterial Hypertension
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical research study to evaluate the safety of changing from Flolan
    to a new drug called Epoprostenol-Actelion in patients suffering from
    pulmonary arterial hypertension
    Studio clinico per valutare la sicurezza del passaggio da Flolan ad un nuovo farmaco chimato Epoprostenol-Actelion in pazienti con ipertensione arteriosa polmonare.
    A.3.2Name or abbreviated title of the trial where available
    EPITOME-2
    EPITOME-2
    A.4.1Sponsor's protocol code numberAC-066A301
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorActelion Pharmaceuticals Ltd.
    B.1.3.4CountrySwitzerland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportActelion Pharmaceuticals Ltd
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationActelion Pharmaceuticals Ltd
    B.5.2Functional name of contact pointGlobal Medical Information
    B.5.3 Address:
    B.5.3.1Street AddressGewerbestrasse 16
    B.5.3.2Town/ cityAllschwill
    B.5.3.3Post code4123
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number+41 61 565 65 65
    B.5.5Fax number+41 61 565 65 00
    B.5.6E-mailmedinfo_ch@actelion.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Epoprostenolo per iniezione
    D.2.1.1.2Name of the Marketing Authorisation holderActelion Pharmaceutical Ltd
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Powder for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEpoprostenol
    D.3.9.1CAS number 61849-14-7
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Epoprostenol for injection
    D.2.1.1.2Name of the Marketing Authorisation holderActelion Pharmaceutical Ltd
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Powder for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEpoprostenol
    D.3.9.1CAS number 61849-14-7
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Pulmonary Arterial Hypertension
    Ipertensione arteriosa polmonare
    E.1.1.1Medical 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
    ipertensione arteriosa polmonare è una condizione in cui la pressione nei vasi sanguigni che vanno ai polmoni (le arterie polmonari) è superiore rispetto al normale
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10064911
    E.1.2Term Pulmonary arterial hypertension
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • To evaluate the change in cardiac hemodynamics from baseline to 3-month following switch from Flolan to EFI on in patients with pulmonary arterial hypertension (PAH). • To evaluate the safety and tolerability of switching from Flolan to EFI in patients with PAH.
    • Valutare il cambiamento nell'emodinamica cardiaca dalla baseline a 3 mesi dopo il passaggio da Flolan ad Epoprostenol per iniezione in pazienti con ipertensione arteriosa polmonare. • Valutare la sicurezza e la tollerabilita' del passaggio da Flolan ad Epoprostenol per iniezione in pazienti con ipertensione arteriosa polmonare.
    E.2.2Secondary objectives of the trial
    E.2.3Trial contains a sub-study No
    E.3Principal 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
    1. Sesso maschile o femminile, eta' minima 18 anni 2. Pazienti con i seguenti tipi di ipertensione arteriosa polmonare appartenenti al gruppo I OMS: • Idiopatici (IPAH) • Ereditari (HPAH) • Associati (APAH) a o Patologie del tessuto connettivo o Farmaci e tossine 3. Pazienti trattati con Flolan per almeno 12 mesi e con una dose stabile per almeno 3 mesi prima dell'arruolamento 4. I pazienti che sono attualmente trattati con terapia concomitante per l'ipertensione arteriosa polmonare elencata nel seguito devono essere stati trattati per almeno 90 giorni e con una dose stabile per 30 giorni prima dell'arruolamento: • Bosentan • Ambrisentan • Sitaxentan • Sildenafil • Tadalafil 5. Le donne in grado di concepire devono utilizzare un metodo di contraccezione affidabile 6. Consenso informato firmato prima dell'inizio di qualsiasi procedura obbligatoria per lo studio
    E.4Principal 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 formulation 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 inclusion 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
    1. Pazienti con disturbi respiratori e/o cardiovascolari con esigenza di cure di emergenza 2. Patologia venocclusiva polmonare nota o sospetta 3. Utilizzo attuale di agenti inotropici endovenosi 4. Utilizzo attuale di qualsiasi prostaciclina o analogo della prostaciclina diversi dal Flolan 5. Tachicardia con frequenza cardiaca &gt; 120 battiti/min a riposo 6. Ipertensione arteriosa polmonare correlata a qualsiasi condizione diversa da quelle specificate nei criteri di inclusione 7. Ipersensibilita' nota alle formulazioni Epoprostenol per iniezione o a qualsiasi suo eccipiente e al Flolan o a qualsiasi suo eccipiente 8. Eventi cerebrovascolari (ad es. attacco ischemico transitorio o ictus) entro 6 mesi dallo screening 9. Anamnesi di infarto del miocardio 10. Anamnesi di patologia cardiaca del lato sinistro, compresa una qualsiasi delle seguenti: • patologia emodinamicamente significativa della valvola aortica o della valvola mitrale • cardiomiopatia restrittiva o congestizia • frazione di eiezione ventricolare sinistra &lt; 40% secondo quanto evidenziato da angiogramma MUGA, angiografia o ecocardiografia • angina pectoris instabile • aritmie cardiache pericolose per la vita 11. Disturbi cronici da sanguinamento 12. Infezione della linea venosa centrale entro 90 giorni prima dello screening e/o anamnesi di infezioni di linea recidive 13. Donne in gravidanza o in allattamento al seno 14. Partecipazione ad un altro trial clinico, tranne quelli di osservazione, oppure ricevimento di un prodotto di ricerca entro 30 giorni prima dell’arruolamento 15. Qualsiasi fattore o patologia noti che possano interferire con la conformita' al trattamento, la condotta dello studio o l'interpretazione dei risultati, ad esempio dipendenza da farmaci o da alcool o disturbi psichiatrici 16. Patologia concomitante nota pericolosa per la vita, diversa dall'ipertensione arteriosa polmonare, con aspettativa di vita &lt; 12 mesi
    E.5 End points
    E.5.1Primary 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)
    Endpoints di tollerabilita'/sicurezza • Eventi avversi in conseguenza del trattamento fino a 24 ore dopo la fine del trattamento • Cambiamento dalla baseline alla fine del trattamento nei segni vitali (frequenza cardiaca e pressione ematica) e nel peso corporeo • Eventi avversi che portano all’interruzione prematura del farmaco dello studio .Eventi avversi gravi in conseguenza del trattamento fino a 30 giorni dopo la fine del trattamento Endpoint di efficacia • Cambiamento dalla baseline alla fine del trattamento nell'emodinamica cardiaca comprendente: o Resistenza vascolare polmonare o Pressione arteriosa polmonare media o Pressione atriale destra o Pressione di occlusione dell'arteria polmonare o Indice cardiaco
    E.5.1.1Timepoint(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
    -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
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability, explaratory study phase 3b
    Tollerabilita', ''explaratory'' studio di fase 3b
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.2.3.1Comparator description
    - Stesso farmaco ad altro dosaggio
    - same IMP used at different dosage
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA6
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    E.8.7Trial 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
    Last Patient Last End of treatment visit
    Last Patient Last End of treatment visit
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months12
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months21
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 35
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 40
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2011-05-04
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-04-12
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2012-02-02
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