Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   42758   clinical trials with a EudraCT protocol, of which   7042   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2015-002078-19
    Sponsor's Protocol Code Number:AC-055-405
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-08-05
    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 ConcernedFrance - ANSM
    A.2EudraCT number2015-002078-19
    A.3Full title of the trial
    Prospective, multicenter, open-label study evaluating the effects of first-line oral combination therapy of macitentan and tadalafil in patients with newly diagnosed pulmonary arterial hypertension.
    Etude prospective, multicentrique, en ouvert, évaluant les effets de l'association thérapeutique en 1ère ligne du macitentan et du tadalafil par voie orale chez des patients avec HTAP nouvellement diagnostiquée
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Prospective, multicenter, open-label study evaluating the effects of first-line oral combination therapy of macitentan and tadalafil in patients with newly diagnosed pulmonary arterial hypertension
    Etude prospective, multicentrique, en ouvert, évaluant les effets de l'association thérapeutique en 1ère ligne du macitentan et du tadalafil par voie orale chez des patients avec HTAP nouvellement diagnostiquée
    A.3.2Name or abbreviated title of the trial where available
    OPTIMA
    OPTIMA
    A.4.1Sponsor's protocol code numberAC-055-405
    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 France
    B.1.3.4CountryFrance
    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 France
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationACTELION Pharmaceuticals France
    B.5.2Functional name of contact pointVirginie Gressin
    B.5.3 Address:
    B.5.3.1Street Address21 boulevard de la Madeleine
    B.5.3.2Town/ cityParis
    B.5.3.3Post code75001
    B.5.3.4CountryFrance
    B.5.4Telephone number00330158623235
    B.5.5Fax number00330158623222
    B.5.6E-mailvirginie.gressin@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 Opsumit
    D.2.1.1.2Name of the Marketing Authorisation holderActelion Registration Ltd
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/11/909
    D.3 Description of the IMP
    D.3.1Product namemacitentan
    D.3.2Product code ACT-064992
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMACITENTAN
    D.3.9.1CAS number 441798-33-0
    D.3.9.2Current sponsor codeACT-064992
    D.3.9.3Other descriptive nameOpsumit
    D.3.9.4EV Substance CodeSUB89247
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 Adcirca
    D.2.1.1.2Name of the Marketing Authorisation holderEli Lilly Nederland B.V.
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    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.3.1Product nametadalafil
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTADALAFIL
    D.3.9.1CAS number 171596-29-5
    D.3.9.3Other descriptive nameAdcirca
    D.3.9.4EV Substance CodeSUB12602MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number20 to 40
    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
    Hypertension artérielle pulmonaire
    E.1.1.1Medical condition in easily understood language
    Pulmonary arterial hypertension
    Hypertension artérielle pulmonaire
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    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 document the effect of first line dual oral combination therapy with macitentan 10mg and tadalafil 40mg on pulmonary vascular resistance (PVR) in treatment-naïve patients with newly diagnosed pulmonary arterial hypertension (PAH).
    Evaluer les effets sur les résistances vasculaires pulmonaires (RVP) de l'association thérapeutique, en première ligne, du macitentan 10mg et du tadalafil 40mg, administrés par voie orale, chez les patients avec une hypertension artérielle pulmonaire (HTAP) nouvellement diagnostiquée, naïfs de tous traitements spécifiques de l’HTAP.
    E.2.2Secondary objectives of the trial
    To document the effect of a first line dual oral combination therapy with macitentan 10mg and tadalafil 40mg on cardio-pulmonary hemodynamic parameters other than PVR, on exercise capacity and disease severity, on NT-proBNP and on safety and tolerability in treatment-naïve patients with newly diagnosed PAH.
    Evaluer, chez les patients avec une hypertension artérielle pulmonaire (HTAP) nouvellement diagnostiquée, naïfs de tous traitements spécifiques de l’HTAP, les effets de l'association thérapeutique, en première ligne, du macitentan 10mg et du tadalafil 40mg, administrés par voie orale, sur les paramètres hémodynamiques cardio-pulmonaires autres que les RVP, sur la capacité à l'exercice du patient, sur le taux de NT-proBNP et sur la tolérance du traitement.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Signed informed consent prior to any study-mandated procedure.
    2. Male or female ≥ 18 and ≤ 75 years of age at screening.
    3. Initial PAH diagnosis < 6 months prior to Day 1.
    4. Right heart catheterization (RHC) performed between Day -28 and Day 1 (RHC data obtained at the study site within this time frame, but before the study, i.e., before signed informed consent, are acceptable), meeting all the following criteria:
    •Resting mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg.
    •Pulmonary capillary wedge pressure (PCWP) or left ventricular end diastolic pressure (LVEDP) ≤ 15 mmHg.
    •PVR ≥ 400 dyn·sec/cm5 (≥ 5 Wood units) if PCWP < 12 mmHg OR PVR ≥ 500 dyn·sec/cm5 (≥ 6.25 Wood units) if PCWP in [12-15] mmHg.
    •Negative vasoreactivity test mandatory in idiopathic PAH (at this or a previous RHC).
    5. World Health Organization (WHO) Functional Class (FC) II to III.
    6. PAH etiology belonging to one of the following groups:
    •Idiopathic.
    •Heritable.
    •Anorexigens induced.
    •Associated with one of the following:
    o Connective tissue disease
    o Congenital heart disease with simple systemic-to-pulmonary shunt (atrial septal defect, ventricular septal defect, patent ductus arteriosus) ≥ 1 year after surgical repair
    o HIV infection
    7. 6MWD ≥ 50 m at screening.
    8. Women of childbearing potential [defined in Section 4.5.1] must:
    • Have a negative serum pregnancy test at the screening visit and a negative urine pregnancy test at the Day 1 visit, and
    • Agree to perform monthly pregnancy tests up to 30 days after EOT2, and
    • Agree to use reliable contraception [defined in Section 4.5.2] from screening up to 30 days after EOT2. Reliable contraception must be started at least 11 days prior to Day 1.
    1. Note d'information et formulaire de consentement signé avant toute procédure liée à l'étude
    2. Homme ou femme âgé de 18 à 75 ans, lors de la visite de sélection
    3. Dont l’HTAP a été diagnostiquée < 6 mois avant Jour 1
    4. Cathétérisme cardiaque droit réalisé entre J -28 et J1 (les données d’un cathétérisme cardiaque droit réalisé, sur le site de recherche, au cours de cette période, avant le démarrage de l'étude, soit avant la signature du formulaire de consentement par le patient peuvent être utilisées), répondant aux critères suivants:
    •Pression artérielle pulmonaire moyenne (PAPm) de repos ≥ 25mmHg.
    •Pression capillaire pulmonaire (PCWP) ou Pression télédiastolique ventriculaire gauche ≤ 15mmHg.
    •Résistances vasculaires pulmonaires (RVP) ≥ 400 dyn.sec/cm5 (≥ 5 unités Wood) si PCWP < 12 mmHg ou RVP ≥ 500 dyn.sec/cm5 (≥ 6.25 unités Wood) si PCWP entre 12 et 15 mmHg, bornes incluses.
    •Test de vasoréactivité négatif obligatoire en cas d'HTAP Idiopathique (réalisé lors du cathétérisme cardiaque droit de l’étude ou préalablement).
    5. Classe fonctionnelle OMS II ou III.
    6. HTAP appartenant à l’un des groupes suivants :
    •Idiopathique
    •Familiale
    •Induite par des anorexigènes
    •Associée à:
    o Une maladie du tissu conjonctif
    o Une cardiopathie congénitale avec shunt gauche droit simple (communication inter-auriculaire, communication inter-ventriculaire, Persistance du canal artériel) persistant ≥ 1 an après chirurgie correctrice.
    o Une infection par le VIH
    7. Test de marche de 6 minutes ≥ 50m lors de la visite de sélection
    8. Pour les femmes en âge de procréer :
    •Test de grossesse sanguin négatif lors de la visite de sélection et test de grossesse urinaire négatif lors de la visite Jour 1
    •Acceptant de réaliser un test de grossesse tous les mois jusqu'à 30 jours après l'arrêt du traitement.
    •Acceptant d’utiliser un moyen contraceptif fiable entre la visite de sélection et jusqu'à 30 jours après la fin du traitement. Une contraception fiable doit être démarrée au moins 11 jours avant Jour1.
    E.4Principal exclusion criteria
    1. Any PAH-specific drug therapy [e. g. any endothelin receptor antagonist, phosphodiesterase-5 inhibitors (PDE-5i), soluble guanylate cyclase stimulator, prostacyclin, prostacyclin analog, or prostacyclin receptor agonist] at any time prior to Day 1 (single-dose administration for vasoreactivity testing is permitted; previous iloprost used intermittently for the treatment of digital ulcers or Raynaud’s phenomenon is permitted if stopped > 6 months prior to Day 1).
    2. Subjects who changed the dose or discontinued calcium channel blockers within 3 months prior to Day 1.
    3. Initiation of diuretics within 1 week prior to RHC.
    4. Subjects on oral diuretics in whom the dose has not been stable for at least 1 week prior to RHC.
    5. Treatment with other PDE-5i for erectile dysfunction.
    6. Treatment with strong inducers of CYP3A4 (e.g., carbamazepine, rifampin, rifampicin, rifabutin, rifapentin, phenobarbital, phenytoin, and St. John’s wort) ≤ 28 days prior to Day 1.
    7. Treatment with strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, boceprevir, telaprevir, saquinavir, lopinavir, fosamprenavir, darunavir, tipranavir, atazanavir, nelfinavir, amprenavir, indinavir) ≤ 28 days prior to Day 1.
    8. History of priapism.
    9. Significant aortic and mitral valve disease.
    10. Pericardial constriction.
    11. Significant left ventricular dysfunction in the opinion of the investigator.
    12. Life-threatening arrhythmia.
    13. Uncontrolled hypertension.
    14. Symptomatic coronary artery disease.
    15. Cardio-pulmonary rehabilitation program based on exercise (planned, or started ≤ 12 weeks prior to Day 1).
    16. Body mass index (BMI) > 40 kg/m2 at screening.
    17. Acute myocardial infarction ≤ 12 weeks prior to Day 1.
    18. Known permanent atrial fibrillation.
    19. Low blood pressure < 90/50 mmHg at screening or Day 1.
    20. Ongoing or planned treatment with nitrates and/or doxazosin.
    21. Presence of ≥ 1 of the following signs of relevant lung disease at any time prior to Day 1:
    •DLCO < 40% of predicted value;
    •FEV1/FVC < 70% and FEV1 < 65% of predicted after bronchodilator administration;
    •Total Lung Capacity (TLC) < 60% of predicted.
    22. Known or suspicion of pulmonary veno-occlusive disease (PVOD).
    23. Severe renal insufficiency (estimated creatinine clearance ≤ 30 mL/min/1.73m²) assessed by central laboratory at screening
    24. Ongoing or planned dialysis.
    25. Documented severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin > 3 x ULN accompanied by AST > ULN (assessed by central laboratory at screening); and/or Child Pugh Class C.
    26. Serum AST and/or ALT > 3 x ULN (assessed by central laboratory at screening).
    27. Porto-pulmonary hypertension.
    28. Hemoglobin < 100 g/L assessed by central laboratory at screening.
    29. Hypersensitivity to any active substance or excipient of macitentan or tadalafil formulation.
    30. Loss of vision in one eye because of non-arteritic anterior ischemic optic neuropathy (NAION), regardless of whether or not this episode was in connection with previous PDE-5i exposure.
    31. Hereditary degenerative retinal disorders, including retinitis pigmentosa.
    32. Pregnancy, breast-feeding, intention to become pregnant during the study or woman of childbearing potential not agree to use reliable method of contraception from screening up to 30 days after EOT2.
    33. Hereditary problems of galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption.
    34. Any factor or condition likely to affect protocol compliance of the patient as judged by the investigator.
    35. Treatment with another investigational drug (planned, or taken ≤ 12 weeks prior to Day 1).
    36. Concomitant life-threatening disease with a life expectancy < 12 months.
    1. Prise d'un traitement pour l'HTAP [ex. antagoniste au récepteur à l'endothéline, inhibiteur de la phosphodiestérase-5 (PDE-5i), stimulateur de la guanylate cyclase soluble, agoniste de la prostacycline, analogue de la prostacycline ou des récepteurs à la prostacycline] antérieurement à Jour 1 (l'administration d'une dose unique pour le test de vasoréactivité est autorisée ; l’utilisation antérieure d'iloprost, de façon intermittente, pour le traitement d'ulcères digitaux ou du phénomène de Raynaud est autorisée, si le traitement a été stoppé depuis plus de 6 mois avant Jour 1).
    2. Sujets ayant modifié la dose ou arrêté un inhibiteur calcique dans les 3 mois précédant Jour 1.
    3. Instauration d’un traitement diurétique dans la semaine précédant le cathétérisme cardiaque droit.
    4. Sujets sous diurétiques par voie orale dont la dose n’a pas été stable dans la semaine précédant le cathétérisme cardiaque droit.
    5. Prise d’un autre inhibiteur de la PDE-5 pour un dysfonctionnement érectile.
    6. Prise d'un traitement inducteur puissant de la CYP3A4 (carbamazepine, rifampine, rifampicine, rifabutine, rifapentine, phenobarbital, phenytoïne et millepertuis) ≤ 28 jours avant Jour1.
    7. Prise d'un traitement inhibiteur puissant de la CYP3A4 (ex. ketoconazole, itraconazole, voriconazole, clarithromycine, telithromycine, nefazodone, ritonavir, saquinavir, lopinavir, le fosamprenavir, le darunavir, le tipranavir, l'atazanavir, nelfinavir, amprenavir, et indinavir) ≤ 28 jours avant Jour1.
    8. Antécédent de priapisme
    9. Valvulopathie mitrale ou aortique sévère.
    10. Péricardite constrictive
    11. Insuffisance cardiaque gauche selon le jugement de l'investigateur,
    12. Arythmie mettant en danger la vie du sujet.
    13. Hypertension artérielle non contrôlée
    14. Coronaropathie symptomatique
    15. Programme de réadaptation cardio-pulmonaire basé sur l'activité physique (programmé ou démarré ≤ 12 semaines avant Jour 1).
    16. Indice de masse corporelle (IMC) > 40kg/m² à la sélection
    17. Infarctus du myocarde ≤ 12 semaines avant Jour 1
    18. Fibrillation auriculaire permanente connue
    19. Pression artérielle <90/50mmHg lors de la visite de sélection ou à Jour 1
    20. Prise d'un traitement par nitrates et/ou doxazosine (en cours ou programmé).
    21. Présence d'au moins un des signes suivants de maladie pulmonaire, à tout moment avant Jour 1
    •DLCO < 40% à la valeur prédite;
    •VEMS/CVF < 70% et VEMS < 65% à la valeur prédite après administration d'un bronchodilatateur;
    •CPT < 60% à la valeur prédite.
    22. Maladie pulmonaire veino-occlusive ou suspicion de maladie pulmonaire veino-occlusive
    23. Insuffisance rénale sévère (clairance de la créatinine estimée ≤ 30mL/min/1,73m²) évaluée par un dosage centralisé à la visite de sélection.
    24. Dialyse en cours ou programmée
    25. Insuffisance hépatique sévère avérée (avec ou sans cirrhose) selon les critères du groupe de travail de l'Institut National du Cancer, soit bilirubine totale > 3 x valeur supérieure normale (LSN) associés à SGPT > LSN (dosage centralisé lors de la visite de sélection) ; et/ou index de Child Push de classe C.
    26. Valeurs SGOT et/ou SGPT sanguins > 3 x LSN (dosage centralisé lors de la visite de sélection)
    27. Hypertension porto-pulmonaire
    28. Taux d'hémoglobine <100 g/L (dosage centralisé lors de la visite de sélection)
    29. Hypersensibilité à la substance active ou aux excipients présents dans la formulation de macitentan ou de tadalafil.
    30. Perte de la vision d'un œil en raison d'une neuropathie optique ischémique antérieure non-artéritique, lié ou non à une exposition antérieure à un inhibiteur de la PDE-5.
    31. Maladie rétinienne dégénérative héréditaire, y compris la rétinite pigmentaire
    32. Femmes enceintes, qui allaitent ou femmes ayant l'intention de tomber enceinte pendant l'étude ou femme en âge de procréer refusant l'utilisation d’une méthode contraceptive fiable jusqu'à 30 jours après EOT2
    33. Intolérance au lactose, déficit en lactase de Lapp ou malabsorption du glucose-galactose.
    34. Tout élément qui, selon l'investigateur, serait susceptible d'empêcher le patient de se plier aux exigences du protocole.
    35. Traitement avec un autre médicament expérimental (prévu ou administré ≤ 12 semaines avant le Jour 1)
    36. Maladie concomitante mettant en danger la vie du patient (espérance de vie < 12 mois)
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the ratio of Week 16 to baseline PVR.
    Le critère d'évaluation principal est le rapport RVP (semaine 16 )/ RVP (valeur basale).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline and Week 16
    Valeur basale et semaine 16
    E.5.2Secondary end point(s)
    • Percentage of patients with clinically meaningful improvement of PVR (decrease ≥ 30% from baseline to Week 16).
    • Change from baseline to Week 16 in mean right atrial pressure (mRAP), mean pulmonary arterial pressure (mPAP), cardiac index (CI), total pulmonary resistance (TPR), and mixed venous oxygen saturation (SvO2), all measured at rest.
    • Change from baseline to Week 16 in 6-minute walk distance (6MWD).
    • Change from baseline to Week 16 in WHO functional class.
    • Percentage of patients with improvement/worsening of WHO functional class from baseline to Week 16.
    • Change in NT-proBNP from Baseline to Week 16.
    • Pourcentage de patients avec une amélioration cliniquement significative des RVP (baisse ≥ 30% entre la valeur basale et la semaine 16)
    • Variation entre la valeur basale et la semaine 16 de la pression auriculaire droite moyenne, de la pression artérielle pulmonaire moyenne, de l'index cardiaque, des résistances pulmonaires totales et de la saturation veineuse en oxygène, au repos.
    • Variation entre la valeur basale et la semaine 16 de la distance parcourue au test de marche de 6 minutes
    • Variation entre la valeur basale et la semaine 16 de la classe fonctionnelle OMS
    • Pourcentage de patients ayant une amélioration ou une aggravation de la classe fonctionnelle OMS, entre la valeur basale et la semaine 16.
    • Variation entre la valeur basale et la semaine 16 du taux de NT-proBNP.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Baseline and Week 16
    Valeur basale et semaine 16
    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 No
    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 No
    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) No
    E.7.4Therapeutic use (Phase IV) Yes
    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) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 Yes
    E.8.4.1Number of sites anticipated in Member State concerned17
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    LVLS
    Dernière visite du dernier patient
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months7
    E.8.9.1In the Member State concerned days
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    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: 50
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 10
    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 state60
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    An assessment of drug safety must be performed (either through phone call or visit) 30 days after each study drug discontinuation.
    At the end of the study, patient medical care will be let at the choice of the physician.
    Une évaluation de la sécurité du médicament doit être réalisée (soit par téléphone soit au cours d'une visite médicale) 30 jours après l'arrêt de chacun des médicaments à l'étude.
    A l'issue de la recherche, la prise en charge médicale du patient est laissée au libre choix du médecin.
    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 Decision2015-06-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-10-14
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-09-10
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA