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    The EU Clinical Trials Register currently displays   43853   clinical trials with a EudraCT protocol, of which   7284   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:2011-004106-16
    Sponsor's Protocol Code Number:AC-052-375
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:
    Date on which this record was first entered in the EudraCT database:2012-02-17
    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 number2011-004106-16
    A.3Full title of the trial
    A randomized, prospective, double-blind, placebo-controlled, group sequential multicenter study to assess efficacy, safety, and tolerability of the pediatric formulation of bosentan in children with pulmonary arterial hypertension
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A 5-month research project for children aged from 1 year to 17 years who have high blood pressure in the lung, to see how well bosentan decreases this high blood pressure and improves children's physical capabilities compared to an inactive compound
    A.3.2Name or abbreviated title of the trial where available
    FUTURE 5
    A.4.1Sponsor's protocol code numberAC-052-375
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorActelion pharmaceuticals Ltd
    B.1.3.4CountrySwitzerland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportActelion Pharmaceuticals Ltd.
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationActelion Pharmaceuticals Ltd.
    B.5.2Functional name of contact pointGLOBAL MEDICAL INFORMATION
    B.5.3 Address:
    B.5.3.1Street AddressGewerbestrasse 16
    B.5.3.2Town/ cityAllschwil
    B.5.3.3Post code4123
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number-
    B.5.5Fax number-
    B.5.6E-mailmedinfo@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 Tracleer
    D.2.1.1.2Name of the Marketing Authorisation holderActelion Registration Ltd.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 namebosentan
    D.3.4Pharmaceutical form Dispersible tablet
    D.3.4.1Specific paediatric formulation Yes
    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 INNbosentan
    D.3.9.1CAS number 157212-55-0
    D.3.9.2Current sponsor codeACT-050088
    D.3.9.3Other descriptive nameBOSENTAN MONOHYDRATE
    D.3.9.4EV Substance CodeSUB22249
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number32
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboDispersible 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
    Pulmonary arterial hypertension (PAH) in children
    E.1.1.1Medical condition in easily understood language
    PAH is a deadly disease that causes narrowing of the pulmonary artery, which requires more effort from the heart to pump blood into the lungs, eventually leading to right heart failure.
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10064908
    E.1.2Term Associated with (APAH)
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10064909
    E.1.2Term Idiopathic (IPAH)
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10064910
    E.1.2Term Familial (FPAH)
    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
    The primary objective is to demonstrate that 12 weeks of treatment with either dose (0.5 mg/kg b.i.d or 2 mg/kg b.i.d) of the bosentan dispersible tablet formulation improves PVRi in pediatric patients with PAH, aged from ≥ 1 year to < 17 years.
    E.2.2Secondary objectives of the trial
    The other objectives are to evaluate the following in this patient population:
    - Other hemodynamic variables, WHO functional class, global clinical status, exercise capacity, time to clinical worsening.
    - Tolerability and safety variables.
    - Echocardiographic variables (imaging and Doppler evaluation).
    - The steady-state PK of the bosentan dispersible tablet formulation at doses of 0.5 mg/kg b.i.d. and 2 mg/kg b.i.d.
    - The PK-efficacy relationship on PVRi and other selected efficacy endpoints.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Signed informed consent by the parents or legal representatives prior to any study mandated procedure.

    2. Male or female ≥ 1 year and < 17 years of age (maximum age
    at randomization is 16 years and 9 months).

    3. WHO functional class I–IV.

    4. PAH diagnosed with Right Heart Catheterization (RHC).

    5. PAH etiologies:
    Idiopathic or heritable PAH,
    or
    Associated PAH persisting/recurrent for at least 6 months
    after complete repair of a congenital heart defect,
    or
    CHD (PAH associated with systemic-to-pulmonary shunts
    including Eisenmenger syndrome).

    6. PVR > 3 Wood units for idiopathic, heritable PAH or PAH
    persisting/recurrent after complete repaired of congenital
    heart defect.
    or
    PVR > 8 Wood units for PAH associated with systemic-to-pulmonary open shunts with a ratio Qp/Qs < 2.

    7. Body weight ≥ 8 kg and ≤ 95 kg.

    8. Patients naïve to PAH-specific treatment
    or
    Patients already treated with PAH-specific medication at a stable dose since at least 3 months:
    Prostanoids, PDE-5 inhibitors
    No combination of PAH-specific therapy is allowed.

    9. Patients naïve to PAH related, non-specific medication
    or
    Patients already treated with PAH related, non-specific medication, such as
    Calcium channel blockers (stable dose since at least 3 months)
    Anticoagulants
    Diuretics
    Digoxin

    10. Females of childbearing potential must have a negative
    pre-treatment pregnancy test and must use reliable methods of
    contraception during the whole treatment period and for 1 month after study drug discontinuation.
    E.4Principal exclusion criteria
    1. Non-stable disease status, e.g., history of recurrent (near-)
    syncope or signs and symptoms of non-compensated right heart failure.

    2. Patients with bronchopulmonary dysplasia, congenital
    diaphragmatic hernia or other chronic lung diseases.

    3. Need or plan to wean patient from any PAH-specific therapies
    during the study.

    4. Systolic blood pressure < 80% of the lower limit of normal
    range.

    5. Aspartate aminotransferase (AST) and/or alanine
    aminotransferase (ALT) values > 1.5 times the upper limit of
    normal range.

    6. Moderate or severe hepatic impairment (i.e., Child-Pugh Class
    B or C).

    7. Hemoglobin and/or hematocrit levels < 75% of the lower limit
    of normal range.

    8. Known intolerance or hypersensitivity to bosentan or any of
    the excipients of the bosentan dispersible tablet.

    9. Treatment with bosentan or any other endothelin receptor
    antagonists within 4 months prior to randomization (including any ERA investigational drug).

    10. Treatment with another investigational drug within 1 month
    prior to randomization or planned treatment.

    11. Pregnancy or breastfeeding.

    12. Any condition that prevents compliance with the protocol or
    adherence to therapy.

    13. Administration of prohibited medication within 2 weeks or
    5 times the half-life, prior to randomization, whichever is the
    longest.
    E.5 End points
    E.5.1Primary end point(s)
    Primary efficacy endpoint = PVRi at Week 12 expressed as percent change from the baseline value.
    ‘baseline’ is defined as the last assessment performed prior to first study drug intake.
    E.5.1.1Timepoint(s) of evaluation of this end point
    See above
    E.5.2Secondary end point(s)
    Secondary efficacy endpoints = Change from baseline to Week 12 in RHC variables.
    E.5.2.1Timepoint(s) of evaluation of this end point
    See above
    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 Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Tolerability
    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 No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Prospective, group sequential
    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.8.2.4Number of treatment arms in the trial3
    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 Yes
    E.8.5.1Number of sites anticipated in the EEA7
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Bulgaria
    Chile
    China
    Colombia
    Croatia
    France
    Guatemala
    India
    Malaysia
    Mexico
    Netherlands
    Peru
    Philippines
    Portugal
    Russian Federation
    Serbia
    Singapore
    South Africa
    Taiwan
    Ukraine
    United States
    Vietnam
    E.8.7Trial has a data monitoring committee Yes
    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
    End of Study is defined as the date on which the last randomized
    patient, not prematurely withdrawn, completes the 12-week treatment and the 7-day AE follow-up period.
    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 days0
    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 days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 105
    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) Yes
    F.1.1.4.1Number of subjects for this age range: 7
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 65
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 33
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    A pediatric patient is legally unable to provide informed consent.
    Therefore, fully informed consent should be obtained from parent(s) or legal representative(s) in accordance with national laws or regulations.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state4
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 37
    F.4.2.2In the whole clinical trial 105
    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)
    For patients who complete the End of Study visit while bosentan treatment is still ongoing, participation in an optional follow-up 1-year extension study under a separate protocol will be available. Those patients not entering the extension will have the 60-day posttreatment follow-up.
    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 Decision2012-02-14
    N.Ethics Committee Opinion of the trial application
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion
    P. End of Trial
    P.End of Trial Status
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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
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