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   42585   clinical trials with a EudraCT protocol, of which   7011   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:2016-001067-36
    Sponsor's Protocol Code Number:18588
    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:2020-11-05
    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 number2016-001067-36
    A.3Full title of the trial
    A prospective, randomized, international, multicenter, double-arm, controlled, open-label study of Riociguat in patients with pulmonary arterial hypertension (PAH) who are on a stable dose of phosphodiesterase-5 inhibitors (PDE-5i) with or without endothelin receptor antagonist (ERA), but not at treatment goal
    Studio prospettico, randomizzato, internazionale, multicentrico, a due bracci, controllato, in aperto su riociguat in pazienti affetti da ipertensione arteriosa polmonare (PAH) in trattamento con una dose stabile di inibitori della fosfodiesterasi 5 (PDE-5i) con o senza antagonista del recettore dell'endotelina (ERA), che non hanno raggiunto l'obiettivo del trattamento.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to find out whether some PAH patients may benefit by replacing their current hosphodiesterase-5 inhibitors (PDE-5i) with or without endothelin receptor antagonist (ERA), with Riociguat
    Uno studio per scoprire se alcuni pazienti con pressione arteriosa polmonare (PAH) possono trarre beneficio sostituendo il loro attuale inibitore della fosfodiesteras-5 (PDE-5i), con o senza antagonista del recettore dell'endotelina (ERA), con Riociguat
    A.3.2Name or abbreviated title of the trial where available
    Riociguat rEplacing PDE-5i therapy evaLuated Against Continued PDE-5i thErapy
    Riociguat in sostituzione della terapia a base di PDE-5i valutato rispetto alla terapia a base di PD
    A.4.1Sponsor's protocol code number18588
    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 SponsorBAYER AG
    B.1.3.4CountryGermany
    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 supportBayer AG
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBayer AG
    B.5.2Functional name of contact pointBayer Clinical Trials Contact
    B.5.3 Address:
    B.5.3.1Street AddressN/A
    B.5.3.2Town/ cityBerlino
    B.5.3.3Post code13342
    B.5.3.4CountryGermany
    B.5.4Telephone number-
    B.5.5Fax number-
    B.5.6E-mailclinical-trials-contact@bayer.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 ADEMPAS - 1 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER (PP/ALU) - 42 COMPRESSE
    D.2.1.1.2Name of the Marketing Authorisation holderBAYER PHARMA AG
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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/3/07/518
    D.3 Description of the IMP
    D.3.1Product nameAdempas¿ 1.0
    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 INNRiociguat
    D.3.9.1CAS number 625115-55-1
    D.3.9.2Current sponsor codeBAY63-2521
    D.3.9.3Other descriptive nameRiociguat
    D.3.9.4EV Substance CodeSUB32880
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 ADEMPAS - 1,5 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER (PP/ALU) - 42 COMPRESSE
    D.2.1.1.2Name of the Marketing Authorisation holderBAYER PHARMA AG
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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/3/07/518
    D.3 Description of the IMP
    D.3.1Product nameAdempas¿ 1.5 mg
    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 INNRiociguat
    D.3.9.1CAS number 625115-55-1
    D.3.9.2Current sponsor codeBAY63-2521
    D.3.9.3Other descriptive nameRIOCIGUAT
    D.3.9.4EV Substance CodeSUB32880
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 3
    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 ADEMPAS - 0,5 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER (PP/ALU) - 42 COMPRESSE
    D.2.1.1.2Name of the Marketing Authorisation holderBAYER PHARMA AG
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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/3/07/518
    D.3 Description of the IMP
    D.3.1Product nameAdempas¿ 0.5 mg compressa rivestita con film
    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 INNRiociguat
    D.3.9.1CAS number 625115-55-1
    D.3.9.2Current sponsor codeBAY63-2521
    D.3.9.3Other descriptive nameRIOCIGUAT
    D.3.9.4EV Substance CodeSUB32880
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 4
    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 ADEMPAS - 2 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER (PP/ALU) - 42 COMPRESSE
    D.2.1.1.2Name of the Marketing Authorisation holderBAYER PHARMA AG
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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/3/07/518
    D.3 Description of the IMP
    D.3.1Product nameAdempas¿ 2.0 mg
    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 INNRiociguat
    D.3.9.1CAS number 625115-55-1
    D.3.9.2Current sponsor codeBAY63-2521
    D.3.9.3Other descriptive nameRiociguat
    D.3.9.4EV Substance CodeSUB32880
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 5
    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 ADEMPAS - 2,5 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER (PP/ALU) - 42 COMPRESSE
    D.2.1.1.2Name of the Marketing Authorisation holderBAYER PHARMA AG
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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/3/07/518
    D.3 Description of the IMP
    D.3.1Product nameAdempas¿ 2.5 mg
    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 INNRiociguat
    D.3.9.1CAS number 625115-55-1
    D.3.9.2Current sponsor codeBAY63-2521
    D.3.9.3Other descriptive nameRIOCIGUAT
    D.3.9.4EV Substance CodeSUB32880
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 6
    D.1.2 and D.1.3IMP RoleComparator
    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 - 20 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER(ALL/PVC/PE/PCTFE) 56 COMPRESSE
    D.2.1.1.2Name of the Marketing Authorisation holderELI LILLY NEDERLAND BV
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameADCIRCA 20 mg
    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.3.9.2Current sponsor codeNA
    D.3.9.3Other descriptive nameTADALAFIL
    D.3.9.4EV Substance CodeSUB12602MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 7
    D.1.2 and D.1.3IMP RoleComparator
    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 REVATIO - 20 MG COMPRESSA RIVESTITA CON FILM 90 COMPRESSE IN BLISTER PVC/ALU
    D.2.1.1.2Name of the Marketing Authorisation holderPFIZER LIMITED
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameRevatio 20 mg
    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 INNSILDENAFIL CITRATE
    D.3.9.1CAS number 171599-83-0
    D.3.9.2Current sponsor codeNA
    D.3.9.4EV Substance CodeSUB04386MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    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 (PAH)
    Ipertensione arteriosa polmonare (PAH)
    E.1.1.1Medical condition in easily understood language
    Pulmonary Arterial Hypertension (PAH)
    Ipertensione arteriosa polmonare
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    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 No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the proportion of patients in each treatment arm with a satisfactory clinical response as defined by a composite primary endpoint at Week 24.
    Valutare la percentuale di pazienti in ogni braccio di trattamento con una risposta clinica soddisfacente, definita come un endpoint primario composito alla settimana 24
    E.2.2Secondary objectives of the trial
    To demonstrate safety and clinical effect at Week 24 indicated by change in 6-minute walking distance (6MWD), N-terminal pro-brain natriuretic peptide (NT-proBNP), World Health Organization Functional Class (WHO FC) and clinical worsening from baseline in each treatment arm.
    Dimostrare la sicurezza e l'efficacia clinica alla settimana 24 indicata dal cambiamento del test del cammino in 6 minuti (6MWD), del valore del frammento N-terminale del propeptide natriuretico di tipo B (NT-proBNP), della classe funzionale dell'OMS (CF OMS) e dal peggioramento clinico dal momento iniziale in ogni braccio di trattamento.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male and female patients aged 18 to 75 years.
    2. Patients with symptomatic PAH with a pulmonary vascular resistance (PVR) > 400 dyn*sec*cm-5, mean pulmonary artery pressure = 25 mmHg, and pulmonary capillary wedge pressure (PCWP) = 15 mmHg as assessed by the most recent right heart catheterization (RHC) from medical history within 12 months prior to screening to confirm the diagnosis. Alternatively, PCWP can be replaced by left ventricular end-diastolic pressure (= 15 mmHg).
    PAH of the following types:
    a. Idiopathic
    b. Hereditary
    c. Drug and toxin induced PAH
    d. Associated with PAH due to:
    - Connective tissue disease (CTD)
    - Congenital heart disease, but only if the patient underwent surgical repair more than one year before enrolment
    - Portal hypertension with liver cirrhosis (Note: patients with clinical relevant hepatic dysfunction are excluded; see exclusions related to disorders in organ function)
    3. Patients who are on stable doses of a PDE-5i and ERA combination therapy or on stable PDE-5i monotherapy 6 weeks prior to and at randomization but not at treatment goal (tadalafil 20 to 40 mg once
    daily or sildenafil at least 60 mg daily dose).
    4. WHO FC III at screening and at randomization.
    5. 6MWD test between 165 m and 440 m at screening and at randomization.
    6. Stable dose of diuretics, if used, for at least 30 days prior to and at randomization.
    7. Patients who are able to understand and follow instructions and who are able to participate in the study for the entire study.
    8. Women of childbearing potential must agree to use adequate contraception when sexually active. Adequate contraception is defined as any combination of at least 2 effective methods of birth control, of which at least 1 is a physical barrier (e.g. condom with hormonal contraception like implants or combined oral contraceptives, condom with intrauterine devices). This applies beginning with signing of the informed consent form until 30 (+5) days after the last administration of study drug.
    9. Patients must have given their written informed consent to participate in the study after having received adequate previous information and
    prior to any study-specific procedures.
    1. maschili e femminili pazienti di età compresa da 18 a 75 anni.
    2. Pazienti con ipertensione arteriosa polmonare sintomatica con una resistenza vascolare polmonare (PVR)> 400 dyn * sec * cm-5, pressione arteriosa polmonare media =25 mmHg e pressione di incuneamento capillare polmonare (PCWP) =15 mmHg, valutata mediante cateterismo cardiaco destro (RHC) della storia clinica nei 12 mesi prima dello screening per confermare la diagnosi. In alternativa, la misurazione di PCWP può essere sostituita dalla pressione telediastolica ventricolare sinistra (= 15 mmHg).
    PAH dei seguenti tipi:
    a. idiopatica,
    b. ereditaria, indotta da farmaco/tossina
    d. associata dovuta a malattia:
    - malattia del tessuto connettivo
    - cardiopatia congenita, ma solo se il paziente è stato sottoposto a riparazione chirurgica più di 1 anno prima dell'arruolamento
    - ipertensione portale con cirrosi epatica (sono esclusi i pazienti con disfunzione epatica clinicamente significativa)
    3. Pazienti in terapia di combinazione con dosi stabili di un PDE-5i ed ERA o in trattamento con PDE-5i stabile in monoterapia da almeno 6 settimane prima e al momento della randomizzazione (tadalafil alla dose giornaliera da 20 a 40 mg o sildenafil alla dose giornaliera di almeno 60 mg).
    4. WHO FC III allo screening e alla randomizzazione.
    5. 6MWD test tra 165 m e 440 m allo screening e alla randomizzazione.
    6. Dose stabile di diuretici, se usati, per almeno 30 giorni prima e alla randomizzazione.
    7. Pazienti in grado di capire e seguire le istruzioni e che possono partecipare per tutto lo studio.
    8. Le donne in età fertile devono accettare di usare un adeguato metodo contraccettivo quando sessualmente attive. Per contraccezione adeguata si intende qualsiasi combinazione di almeno 2 metodi efficaci di controllo delle nascite, di cui almeno 1 è una barriera fisica (ad esempio preservativo con la contraccezione ormonale, come impianti o contraccettivi orali combinati, preservativo con dispositivi intrauterini). Ciò si applica dall’inizio con la firma del modulo di consenso informato fino a 30 (+5) giorni dopo l'ultima somministrazione del farmaco in studio.
    9. Pazienti devono aver dato il loro consenso scritto a partecipare allo studio dopo aver ricevuto adeguate informazioni e prima di qualsiasi procedura studio specifica.
    E.4Principal exclusion criteria
    1. Participation in another interventional clinical study within 30 days prior to screening.
    2. Previous randomization to treatment during this study (no rerandomization).
    3. Previous treatment with riociguat.
    4. Pregnant women, or breast feeding women, or women with childbearing potential not using a combination of 2 effective contraception methods throughout the study.
    5. Patients with a medical disorder, condition, or history of such that would impair the patient's ability to participate or complete this study, in the opinion of the investigator.
    6. Patients with substance abuse (e.g.,alcohol or drug abuse) within the previous 3 months prior to and at randomization.
    7. Patients with underlying medical disorders with an anticipated life expectancy below 2 years (e.g.,active cancer disease with localized and/or metastasized tumor mass).
    8. Patients with a history of severe allergies or multiple drug allergies.
    9. Patients with hypersensitivity to the investigational drug or any of the excipients.
    10. Patients unable to perform a valid 6MWD test (e.g.,orthopedic disease, peripheral artery occlusive disease, which affects the patient's ability to walk).
    11. Participation at a supportive physical training program, defined as a structured exercise and rehabilitation program supervised by a physician
    and/or a physiotherapist within 12 weeks prior to screening. Participants enrolled in an exercise program for pulmonary rehabilitation >
    12 weeks prior to screening may enter the study if they agree to maintain their current level of rehabilitation during the screening and the 24 weeks of the study.
    12. Excluded medication/treatment:
    a. Patients who are screened for possible articipation in the study must
    not be withdrawn from treatments which are medically required. If such treatments are not in-line with the entry criteria of this study, the patient must not be enrolled. Concomitant use with riociguat of the following specific medications for treatment of PAH is not allowed at any time during the study:
    • PDE-5i must not be co-administered with riociguat
    • Non-specific PDE-inhibitors
    • NO donors
    b. Prostacyclin analogues (PCA) and prostacyclin-receptor agonists (PRA) by any administration route within 30 days prior to and at randomization (except for vasoreactivity testing).
    13. Exclusion criteria related to pulmonary disease:
    a. All types of PH (including PH-IIP) except subtypes of Dana Point Group I specified in the inclusion criteria.
    b. Evidence of clinically significant restrictive or obstructive parenchymal lung diseases in the judgment of the investigator
    c. Severe congenital abnormalities of the lungs, thorax, and diaphragm.
    d. Severe restrictive lung disease (total lung capacity [TLC] < 60%).
    e. Moderate obstructive lung disease (forced expiratory volume in one
    second/forced vital capacity [FEV1/FVC] < 50%).
    f. Confirmed obstructive sleep apnea
    g. Severe diffusion impairment (diffusing capacity of the lung for carbon
    monoxide < 30% predicted).
    h. History or active state of serious hemoptysis/pulmonary hemorrhage including those managed by bronchial artery embolization
    1. Partecipazione in un altro studio clinico interventistico nei 30 giorni prima dello screening.
    2. Randomizzazione precedente al trattamento nel corso di questo studio (no ri-randomizzazione).
    3. precedente trattamento con riociguat.
    4. Le donne in gravidanza o donne che allattano al seno, o le donne con età fertile che non utilizzando una combinazione di 2 efficaci metodi di contraccezione sicura.
    5. Pazienti con un disturbo medico, condizione, o la storia di tale condizione che impedirebbero la capacità del paziente di partecipare o completare lo studio, secondo il parere dello sperimentatore.
    6. Pazienti con abuso di sostanze (ad esempio, alcool o droga) nei precedenti 3 mesi prima e alla randomizzazione.
    7. Pazienti con disturbi clinici con aspettativa di vita prevista sotto i 2 anni (ad esempio, tumore attivo con massa localizzata e / o metastasi).
    8. I pazienti con una storia di allergie gravi o multiple allergie ai farmaci.
    9. I pazienti con ipersensibilità al farmaco o a uno qualsiasi degli eccipienti.
    10. I pazienti non in grado di eseguire un valido 6MWD (ad esempio, malattie ortopediche, arteriopatia occlusiva periferica, che colpisce la capacità del paziente di camminare).
    11. La partecipazione a un programma di allenamento fisico di supporto, definito come un programma strutturato di allenamento e riabilitazione sotto la supervisione di un medico e / o un fisioterapista entro 12 settimane prima dello screening.
    I partecipanti arruolati in un programma di esercizi per la riabilitazione polmonare >12 settimane prima dello screening possono partecipare allo studio se accettano di mantenere il loro attuale livello di riabilitazione durante lo screening e le 24 settimane dello studio.
    12. Farmaco / trattamento esclusi:
    a. Pazienti che sono sottoposti a screening per possibili partecipazione nello studio non devono interrompere trattamenti che sono medicalmente necessari. Se tali trattamenti non sono in linea con i criteri di entrata di questo studio, il paziente non deve essere arruolato. L'uso concomitante con riociguat dei seguenti farmaci specifici per il trattamento della PAH non è consentita in qualsiasi momento dello studio:
    • PDE-5i non deve essere co-somministrato con riociguat
    • inibitori PDE non specifici
    • donatori di NO
    b. analoghi della prostaciclina (PCA) e agonisti dei recettori della prostaciclina-(PRA) in qualsiasi via di somministrazione, entro 30 giorni prima e alla randomizzazione (ad eccezione per i tets si vasoreattività).
    13. Criteri di esclusione relativi alla malattia polmonare:
    a. Tutti i tipi di PH (incluso PH-IIP) eccetto i sottotipi di Dana Point Group I definiti nei criteri di inclusione.
    b. evidenza clinicamente significativa di malattie restrittive o ostruttive del parenchima polmonare in base al giudizio dello sperimentatore
    c. Gravi anomalie congenite del polmone, torace e del diaframma.
    d. malattia polmonare restrittiva grave (capacità polmonare totale [TLC] <60%).
    e. malattia polmonare ostruttiva moderata (FEV1 / FVC] <50%).
    f. confermata apnea ostruttiva durante il sonno
    g. Severa insufficienza della capacità di diffusione (la capacità di diffusione del polmone per il monossido <30% del previsto).
    h. Storia o stato attivo di grave emottisi/ emorragia polmonare compresi quelli trattati con embolizzazione dell'arteria bronchiale
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint 'satisfactory clinical response' is defined as the composite endpoint comprising the following components
    (independent central adjudication):
    2 of 3 must be fulfilled
    - 6MWD increase by = 10% or = 30 m from baseline to Week 24
    - WHO FC I or II at Week 24
    - NT-proBNP reduction = 30% from baseline to Week 24 (NT-proBNP
    ratio Week 24/baseline = 0.7), AND
    - No clinical worsening
    L'endpoint primario di efficacia di risposta clinica soddisfacente è definito come l'endpoint composito che comprende i seguenti componenti (giudizio indipendente centrale):
    devono essere soddisfatti 2 su 3
    • aumento =10% o =30 m del risultato del test 6MWD alla settimana 24 rispetto al momento iniziale
    • CF I o II OMS alla settimana 24
    • Riduzione =30% del valore di NT-proBNP alla settimana 24 rispetto al momento iniziale (rapporto NT-proBNP settimana 24/momento iniziale =0,7) E
    • nessun peggioramento clinico
    E.5.1.1Timepoint(s) of evaluation of this end point
    24 weeks
    24 settimane
    E.5.2Secondary end point(s)
    - Change from baseline in 6MWD (blinded assessment)
    - Change from baseline in NT-proBNP
    - Change from baseline in WHO FC (blinded assessment)
    - Clinical worsening
    - Variazione rispetto al basale 6MWD (valutazione in cieco)
    - Variazione rispetto al basale di NT-proBNP
    - Variazione dal basale WHO FC (valutazione in cieco)
    - Peggioramento clinico
    E.5.2.1Timepoint(s) of evaluation of this end point
    24 weeks
    24 settimane
    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 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 Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA54
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Austria
    Belgium
    Brazil
    Canada
    Czechia
    Denmark
    France
    Germany
    Greece
    Italy
    Japan
    Korea, Republic of
    Mexico
    Netherlands
    New Zealand
    Portugal
    Spain
    Switzerland
    Taiwan
    Turkey
    United Kingdom
    United States
    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
    LVLS
    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 months3
    E.8.9.1In the Member State concerned days5
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days5
    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: 164
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 54
    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 state11
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 110
    F.4.2.2In the whole clinical trial 218
    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)
    Standard of Care
    Standard of Care
    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 Decision2016-12-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-12-12
    P. End of Trial
    P.End of Trial StatusCompleted
    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