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    The EU Clinical Trials Register currently displays   44258   clinical trials with a EudraCT protocol, of which   7344   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:2008-004405-34
    Sponsor's Protocol Code Number:GS-US-231-0101
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2009-01-22
    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 ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2008-004405-34
    A.3Full title of the trial
    A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center, Parallel-Group, Event-Driven Study to Evaluate the Efficacy and Safety of Ambrisentan in Subjects with Early Idiopathic Pulmonary Fibrosis (IPF)
    A.3.2Name or abbreviated title of the trial where available
    ARTEMIS-IPF
    A.4.1Sponsor's protocol code numberGS-US-231-0101
    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 SponsorGilead Sciences Incorporated
    B.1.3.4CountryUnited States
    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 Yes
    D.2.1.1.1Trade name Letairis 5 mg
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences Inc
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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.3.4Pharmaceutical 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 INNAmbrisentan
    D.3.9.1CAS number 177036-94-1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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 No
    D.3.11.8Extractive medicinal product No
    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 Yes
    D.2.1.1.1Trade name Letairis 10 mg
    D.2.1.1.2Name of the Marketing Authorisation holderGilead Sciences Inc
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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.3.4Pharmaceutical 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 INNAmbrisentan
    D.3.9.1CAS number 177036-94-1
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) 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 No
    D.3.11.8Extractive medicinal product No
    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
    Idiopathic pulmonary fibrosis (IPF)
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10021240
    E.1.2Term Idiopathic pulmonary fibrosis
    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 of the study is to determine if ambrisentan is effective in delaying disease progression and death in subjects with IPF.
    E.2.2Secondary objectives of the trial
    Secondary objectives include evaluation of the safety and effect of ambrisentan on
    development of pulmonary hypertension, quality of life and dyspnea symptoms in this patient population.

    Exploratory evaluations will include changes in other disease-related assessments including the UNOS LAS, changes in microRNA expression and biomarkers related to IPF pathogenesis. Blood will be collected and stored for later analysis to determine relationships between serum and plasma marker levels and relation to treatment effect and outcomes measures.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or females from 40 to 80 years of age
    2. Diagnosis of Idiopathic Pulmonary Fibrosis (IPF) based on the following criteria in
    accordance with ATS-ERS guidelines for diagnosing IPF:
    — Definite or probable UIP confirmed on SLB by core pathologist
    or
    — In absence of SLB, HRCT scan showing definite findings for IPF (bibasilar
    reticular abnormalities with minimal ground glass opacities) as determined by core
    review
    and three of the following “minor criteria”:
    — Age > 50 years
    — Insidious onset of otherwise unexplained dyspnea on exertion
    — Duration of illness ≥ 3 months
    — Bibasilar, inspiratory crackles
    Within 90 days of study enrollment, diagnosis must be confirmed by HRCT
    3. Honeycombing ≤ 5% as assessed on HRCT; HRCT results will undergo a core review
    process (please see Section 7.4 of the protocol) to confirm diagnosis.
    4. Willingness to undergo RHC at baseline and at Visit 7 or end of study (EOS)
    5. Willingness and ability to comply with required monitoring of liver function every
    28 days. LFTs include serum ALT, AST, alkaline phosphatase, gamma glutamyl
    transferase (GGT), and total bilirubin concentrations
    6. Forced vital capacity (FVC) > 50 to ≤ 95% of predicted with a ratio of
    FEV1 (L) / FVC (L) ≥ 0.7. Pulmonary function tests must be completed no more than
    90 days before enrollment
    7. Ability to perform and complete 6MWT at screening
    8. Negative serum pregnancy test at screening and negative urine pregnancy test at
    randomization for female subjects of childbearing potential (defined in Section 6.3 of the protocol).
    9. Female subjects of childbearing potential must be willing to use at least two reliable
    methods of contraception throughout their participation in the study and 30 days after
    discontinuation of IMP unless the subject has had a tubal sterilization, is
    postmenopausal, or has a Copper T 380A intrauterine device (IUD) or LNg 20 IUD
    inserted, in which case no other contraception is needed. Subjects of childbearing
    potential must also be willing to undergo pregnancy tests every 28 days.
    10. Male subjects must be capable of understanding and acknowledging potential risks of
    testicular tubular atrophy and infertility associated with taking this IMP as described
    in the Informed Consent Form (ICF)
    11. Competency to understand the information given in the Institutional Review Board
    (IRB) or Independent Ethics Committee (IEC) approved ICF. Subjects must sign the
    form prior to the initiation of any study procedures, unless the assessment is
    performed in the routine care for this disease
    E.4Principal exclusion criteria
    1. Diagnosis of an ILD or restrictive lung disease other than UIP or IPF
    2. Obstructive lung disease as determined by evidence of airflow obstruction on HRCT
    or physiologic criteria including:
    • FEV1/FVC ratio < 0.7
    • RV > 120% by plethysmography or significant (verified by radiologist) emphysema on HRCT if plethysmography not available
    • Evidence of reactive airway disease by change in FEV1 of > 12% following bronchodilator challenge

    3. Evidence of sustained improvement of IPF condition defined as improvement from
    pre-therapy PFTs observed with two or more successive post-therapy PFTs over the
    year prior to randomization
    4. Condition(s) that is or are a contraindication for RHC including:
    • Tricuspid or pulmonary valve stenosis
    • Prosthetic tricuspid or pulmonary valve
    • Right atrial or right ventricular masses
    • Cyanotic heart disease
    • Allergy to latex or catheter material
    • Previous pneumonectomy.
    5. Active or recent (≤ 60 days prior to enrollment) pulmonary or upper respiratory tract
    infection
    6. Hospitalization within 60 days of screening for an acute exacerbation of IPF
    (AE-IPF)
    7. Chronic heart failure (NYHA class III/IV) or known left ventricular ejection
    fraction < 25%
    8. Chronic treatment with the following drugs prescribed for IPF (within 4 weeks of
    randomization):oral corticosteroids (> 20 mg/day of prednisone or equivalent),
    immunosuppressive or cytotoxic drugs, antifibrotic drugs, chronic use of Nacetylcysteine
    (prescribed for IPF)
    9. Acute or chronic impairment (other than dyspnea) which limits the ability to comply
    with study requirements and procedures including the 6MWT
    10. Treatment with ambrisentan in a clinical study or with commercial product
    11. Treatment with an approved or experimental ERA within 30 days prior to
    randomization
    12. Chronic use of sildenafil or other phosphodiesterase type 5 (PDE-5) inhibitor for
    pulmonary hypertension
    13. Chronic treatment with immunosuppressive, cytotoxic, or antifibrotic drugs including
    pirfenidone, D-penicillamine, colchicine, TNF-α antagonists, imatinib,
    interferon-gamma, cyclophosphamide, cyclosporine A, or azathioprine within 30 days
    of randomization (Section 5.4 of the protocol)
    14. Prior ERA treatment discontinued for any toxicity
    15. ALT or AST > 1.5 × ULN at screening
    16. Hemoglobin concentration < 75% of LLN at screening
    17. Serum creatinine ≥ 2.5 mg/dL (221 μmol/L) or subject requires hemodialysis,
    peritoneal dialysis or hemofiltration
    18. Systolic blood pressure < 85 mmHg
    19. History of malignancies within the past 5 years, with the exception of basal cell
    carcinoma of the skin or successfully treated in situ carcinoma of the cervix
    20. Female who is pregnant or nursing
    21. Known history of alcohol abuse within 1 year of enrollment
    22. Participation in a clinical study and receiving another investigational drug or device (not placebo) within 28 days of screening
    23. Comorbid condition or illness limiting life expectancy to < 1 year at time of screening
    24. Serious or active medical or psychiatric condition which, in the opinion of the Investigator, would interfere with subject treatment, assessment or compliance with
    the protocol
    E.5 End points
    E.5.1Primary end point(s)
    A composite endpoint of Progression Free Survival (PFS) will be used in this study. The primary endpoint, time to death or disease progression, will be defined as the first incidence of any of the following:
    • Either a decrease of ≥10% in FVC (L) and a decrease of ≥ 5% in diffuse lung capacity for carbon monoxide (DLCO) (ml/min/mmHg) or a decrease of ≥5% in FVC (L) and a decrease of ≥ 15% in DLCO (ml/min/mmHg); (deterioration in FVC and DLCO must be confirmed at the subsequent visit within 28 (± 14) days)

    • Respiratory hospitalization (as defined in Section 7.10 of the protocol).Events will be adjudicated by a blinded Endpoint Committee
    • All-cause mortality.
    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) 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 Yes
    E.8.1.7.1Other trial design description
    Event-Driven
    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 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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA80
    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 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
    Last Patient, last visit.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months9
    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 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 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 state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 260
    F.4.2.2In the whole clinical trial 660
    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 Decision2009-01-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-03-09
    P. End of Trial
    P.End of Trial StatusCompleted
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