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    Summary
    EudraCT Number:2004-000632-82
    Sponsor's Protocol Code Number:AC-052-333
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-02-11
    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 ConcernedUK - MHRA
    A.2EudraCT number2004-000632-82
    A.3Full title of the trial
    Long term bosentan open label extension of the RAPIDS-2 study in Systemic Sclerosis patients with ischemic digital ulcers
    A.3.2Name or abbreviated title of the trial where available
    RAPIDS-2 Open label extension
    A.4.1Sponsor's protocol code numberAC-052-333
    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 AuthorisationUnited Kingdom
    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/3/03/139
    D.3 Description of the IMP
    D.3.1Product namebosentan
    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 INNbosentan monohydrate
    D.3.9.1CAS number 147536-97-8
    D.3.9.2Current sponsor codeRo47-0203/029
    D.3.10 Strength
    D.3.10.1Concentration unit % percent
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number98.0 to 102.0
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    SSc is a multi-system disorder of unknown etiology characterized by fibrosis and vascular obliteration in the skin and visceral organs. The pathogenesis of SSc involves immunologic mechanisms vascular damage and excessive accumulation of fibrosis in the skin and internal organs. As vascular damage progresses the microvascular bed in the skin and other sites is impaired, producing a state of chronic ischemia. SSc is commonly divided into the diffuse and limited form of the disease
    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
    To collect long-term efficacy, tolerability and safety data of bosentan in Systemic Sclerosis (SSc) patients suffering from ischemic digital ulcers (DU).
    E.2.2Secondary objectives of the trial
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    Patients who have completed the full study period (24 to 36-week treatment period and 8-week follow up) of the RAPIDS-2 study.

    Patients who either present DUs at the end of the RAPIDS-2 study period or develop new DUs thereafter until release of the RAPIDS-2 study results to investigators.

    Male or female patients of 18 years of age and older
    - Women of childbearing potential must have a negative pre-treatment pregnancy test and use a reliable method of contraception during study treatment and for at least 3 months after study treatment termination.
    - Women not of childbearing potential are defined as postmenopausal (i.e., amenorrhea for at least 1 year), or surgically or naturally sterile.

    Signed informed consent
    E.4Principal exclusion criteria
    Systolic blood pressure < 85 mmHg.

    Hemoglobin concentration < 75% of the lower limit of the normal range

    AST and/or ALT values greater than 3 times the upper limit of normal

    Pregnancy or breast-feeding

    Body weight < 40 kg

    Patient who received an investigational product within 1 month preceding screening

    Patient with conditions that prevent compliance with the protocol or adhering to therapy

    Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C

    Known hypersensitivity to bosentan or any of the excipients

    Treatment with any of the following: glibenclamide (glyburide), fluconazole, cyclosporine A, tacrolimus and any other calcineurin inhibitor 1 week prior to bosentan treatment
    E.5 End points
    E.5.1Primary end point(s)
    EFFICACY endpoints:

    Total number of new DUs per patient observed by the investigator at planned visits (a patient diary will be used to record DUs that might appear and disappear between two planned visits)

    Time to complete healing of each baseline DU

    Time to complete healing of each new DU

    Change from baseline to each assessment carried out every 16 weeks in the Scleroderma Health Assessment Questionnaire (SHAQ) and in the composite of hand components of the SHAQ: grip, hygiene, dressing and grooming

    Change from baseline to each assessment carried out every 16 weeks in overall hand pain related to finger ulcers

    Change from baseline to each assessment carried out every 16 weeks in UK SSc Functional Score (UKFS)

    If appropriate, exploratory endpoints, derived from the clinical database, will be analyzed based on data-driven considerations.

    SAFETY/TOLERABILITY endpoints:

    Adverse events up to 24 hours after last study medication

    Serious adverse events up to 28 days after last study medication

    AEs leading to permanent discontinuation of the study medication
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Information not present in EudraCT
    E.6.2Prophylaxis Information not present in EudraCT
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Information not present in EudraCT
    E.6.7Pharmacodynamic Information not present in EudraCT
    E.6.8Bioequivalence Information not present in EudraCT
    E.6.9Dose response Information not present in EudraCT
    E.6.10Pharmacogenetic Information not present in EudraCT
    E.6.11Pharmacogenomic Information not present in EudraCT
    E.6.12Pharmacoeconomic Information not present in EudraCT
    E.6.13Others Information not present in EudraCT
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Information not present in EudraCT
    E.7.1.1First administration to humans Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Information not present in EudraCT
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) Information not present in EudraCT
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Information not present in EudraCT
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Information not present in EudraCT
    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.8.5The trial involves multiple Member States Yes
    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
    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
    Treatment duration:

    The study treatment for each patient lasts from his/her enrollment date until the end of the trial. If for example negative RAPIDS-2 results are released, based on the recommendations of the Steering Committee, the present study may be stopped. If RAPIDS-2 results are positive, the present study may be prolonged at the latest up to the commercialization of bosentan in ischemic DUs associated with SSc.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months31
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months32
    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 2005-02-11. 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 Information not present in EudraCT
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 65
    F.4.2.2In the whole clinical trial 180
    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 Decision2004-08-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2004-09-16
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2009-01-16
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