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    The EU Clinical Trials Register currently displays   43846   clinical trials with a EudraCT protocol, of which   7282   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).

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    Summary
    EudraCT Number:2005-001965-33
    Sponsor's Protocol Code Number:AC-052-366
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-09-28
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2005-001965-33
    A.3Full title of the trial
    Estudio prospectivo, aleatorizado, controlado con placebo, doble-ciego, multicéntrico, en grupos paralelos, para evaluar la eficacia, seguridad y tolerabilidad de bosentan en pacientes con hipertensión pulmonar tromboembólica crónica (HPTC) inoperable
    A.3.2Name or abbreviated title of the trial where available
    BENEFIT
    A.4.1Sponsor's protocol code numberAC-052-366
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 Information not present in EudraCT
    D.2.1.1.1Trade name Tracleer
    D.2.1.1.2Name of the Marketing Authorisation holderActelion Registration Ltd
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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/3/01/019
    D.3 Description of the IMP
    D.3.1Product namemonohidrato de bosentan
    D.3.2Product code Ro 47-0203
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNmonohidrato de bosentan
    D.3.9.1CAS number 157212-55-0
    D.3.9.2Current sponsor codeRo-47-0203/029
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number62.5
    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) Information not present in EudraCT
    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 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 Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    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 Information not present in EudraCT
    D.2.1.1.1Trade name Tracleer
    D.2.1.1.2Name of the Marketing Authorisation holderActelion Registration Ltd
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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/3/01/019
    D.3 Description of the IMP
    D.3.1Product namemonohidrato de bosentan
    D.3.2Product code Ro 47-0203
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNmonohidrato de bosentan
    D.3.9.1CAS number 157212-55-0
    D.3.9.2Current sponsor codeRo-47-0203/029
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number125
    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) Information not present in EudraCT
    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 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 Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.8Extractive medicinal product Information not present in EudraCT
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    hipertensión pulmonar tromboembólica crónica (HPTC) inoperable
    MedDRA Classification
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Demostrar que bosentan mejora la capacidad de ejercicio y/o la resistencia vascular pulmonar (PVR) en pacientes con HPTC inoperable
    E.2.2Secondary objectives of the trial
    Evaluar el efecto de bosentan en el tiempo hasta empeoramiento clínico, clase NYHA y hemodinámica cardiaca en pacientes con HPTC inoperable.

    Evaluar la seguridad y tolerabilidad de bosentan en esta población de pacientes.
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    · Hipertensión pulmonar sintomática en clases funcionales NYHA modificadas II a IV por HPTC evidenciada mediante gammagrafía de ventilación / perfusión y angiografía

    · HPTC juzgada inoperable debido a la localización periférica del material trombótico ó hipertensión

    · Hipertensión pulmonar persistente o recurrente tras endarterectomía pulmonar (PEA), sin evidencia de tromboembolismo recurrente, y no apta para reintervención quirúrgica

    · Distancia en el test de la marcha de 6 minutos (6MWT) < 450 m

    · Resultados de evaluación hemodinámica que indiquen:
    i. Presión arterial pulmonar media (mPAP) ≥ 25 mmHg
    ii. Presión de enclavamiento capilar pulmonar (PCWP) < 15 mmHg
    iii. Resistencias vasculares pulmonares (PVR) en reposo ≥300din.seg/cm5
    →Para pacientes sometidos a PEA, la evaluación hemodinámica debe haberse realizado al menos 3 meses después de PEA
    →Para todos los pacientes, la evaluación hemodinámica debe haberse realizado dentro de los 3 meses inmediatamente anteriores a la inclusión

    · Hombres o mujeres con edades de ≥ 18 y ≤ 80 años (las mujeres en edad fértil deberán someterse a tener una prueba de embarazo negativa antes del tratamiento y deberán usar un método anticonceptivo fiable)

    · Anticoagulantes en dosis efectiva durante al menos los 3 meses antes de la aleatorización

    · Firma del consentimiento informado antes de iniciar cualquier procedimiento dictado requerido por el estudio.
    E.4Principal exclusion criteria
    · Otras formas de hipertensión pulmonar incluida la hipertensión pulmonar relacionada con la anemia falciforme.

    · Enfermedad pulmonar obstructiva severa: FEV1/FVC < 0.6.

    · Enfermedad pulmonar restrictiva severa: Capacidad pulmonar total < 60% del valor predicho.

    · Discapacidad aguda o crónica (además de disnea) que limite la capacidad de satisfacer los requisitos del estudio (en particular el criterio 6MWT), p. ej. angina de pecho, claudicación intermitente.

    · Embolismo pulmonar sintomático en los 6 meses anteriores a la aleatorización.

    · Alta hospitalaria por endarterectomía pulmonar en los 3 meses anteriores a la aleatorización.

    · Desorden psicótico, adictivo o de otro tipo que limite la capacidad de otorgar el consentimiento informado o de ceñirse a los requisitos del estudio.

    · Pacientes VIH con infección oportunista.

    · Enfermedad con esperanza de vida inferior a 6 meses.

    · Insuficiencia hepática moderada a grave (grados Child-Pugh B ó C).

    · AST y/o ALT > 3 veces el límite superior de los rangos normales.

    · Concentración de hemoglobina < 75% del límite inferior de los rangos normales.

    · Embarazo o lactancia.

    · Presión sanguínea sistólica < 85 mmHg.

    · Tratamiento o previsión de tratamiento con otro fármaco en investigación y/o angioplastia pulmonar en los 3 meses anteriores a la aleatorización.

    · Tratamiento con antagonistas de los receptores de la endotelina, inhibidores de la fosfodiesterasa, L-arginina o prostanoides (excluyéndose la administración aguda durante un procedimiento de cateterismo para prueba de reactividad vascular) en los 3 meses anteriores a la aleatorización.

    · Tratamiento para la hipertensión pulmonar en el mes anterior a la aleatorización, excepto antagonistas de los canales del calcio, si los hay durante al menos 1 mes antes de la aleatorización.·

    Tratamiento con inhibidores de la calcineurina (p. ej. ciclosporina A y tacrolimus), sirolimus, fluconazol, glibenclamida (gliburida) en la semana previa a la aleatorización.

    · Hipersensibilidad conocida a bosentan o alguno de los excipientes.
    E.5 End points
    E.5.1Primary end point(s)
    There are two Co-Primary Endpoints:

    · Cambio en la distancia recorrida en el 6MWT desde basal a la Semana 16. Se considera clínicamente relevante una diferencia de al menos 35 m respecto al placebo. Se prevé que este parámetro exhiba una distribución normal con una desviación estándar de 65 m.

    · PVR en reposo en la Semana 16 expresada como un porcentaje del valor basal. Se considera clínicamente relevante una media geométrica en el grupo activo que muestre una reducción de al menos el 20% comparada con la media geométrica del placebo. Se prevé que el logaritmo natural de este parámetro exhiba una distribución normal con una desviación estándar de 0.280.
    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 Information not present in EudraCT
    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) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    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) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The 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 Information not present in EudraCT
    E.8.7Trial has a data monitoring committee Information not present in EudraCT
    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
    Último paciente, última visita
    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 months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 Information not present in EudraCT
    F.3.3.1Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2005-09-28. Yes
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    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 state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 76
    F.4.2.2In the whole clinical trial 128
    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)
    Aquellos pacientes que finalicen el estudio según lo previsto en el protocolo, cuando se considere que el tratamiento con bosentan puede resultar beneficioso, podrán participar en un estudio de extensión abierta opcional (con protocolo independiente).
    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 Decision2005-11-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-09-22
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2007-02-07
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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