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The European Union Clinical Trials Register allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   43206   clinical trials with a EudraCT protocol, of which   7151   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.
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    EudraCT Number:2007-006276-11
    Sponsor's Protocol Code Number:VR496/005
    National Competent Authority:Ireland - HPRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2008-02-11
    Trial results View results
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    A. Protocol Information
    A.1Member State ConcernedIreland - HPRA
    A.2EudraCT number2007-006276-11
    A.3Full title of the trial
    A Phase I/II randomised, placebo-controlled, double blind trial to assess the safety, tolerability, pharmacodynamics and exploratory efficacy of heparin 25 mg inhalation powder in adults with Cystic Fibrosis (CF)
    A.3.2Name or abbreviated title of the trial where available
    VR496/005− Orally inhaled heparin in adults with Cystic Fibrosis
    A.4.1Sponsor's protocol code numberVR496/005
    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 SponsorVectura Limited
    B.1.3.4CountryUnited Kingdom
    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.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 No
    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/3/05/337
    D.3 Description of the IMP
    D.3.1Product nameHeparin 25mg inhalation powder, hard capsule
    D.3.4Pharmaceutical form Inhalation powder, hard capsule
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPInhalation use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 9041081
    D.3.10 Strength
    D.3.10.1Concentration unit IU/mg international unit(s)/milligram
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number150
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product Information not present in EudraCT
    D. ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D. 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 Yes
    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 placeboInhalation powder, hard capsule
    D.8.4Route of administration of the placeboInhalation use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Cystic Fibrosis
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10011763
    E.1.2Term Cystic fibrosis lung
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To investigate the safety and tolerability of heparin 25 mg, inhalation powder, hard capsules in adults with CF.
    E.2.2Secondary objectives of the trial
    Pharmacodynamic investigation of: Expectorated mucus (rheological). Effects on sputum inflammatory markers (neutrophil elastase, IL-6, -8, total cell count, %neutrophils,%macrophages); effect on pH in exhaled breath condensate may be measured; on inflammatory blood markers(neutrophil elastase, neutrophil elastase / alpha-1 antitrypsin complex, IL-6, -8, neutrophil count, C reactive protein); coagulation (aPTT, platelets). Evaluate efficacy by VAS based on change in symptoms: cough resolution; expectorated sputum clearability, thickness, volume, colour, viscoelasticity; breathlessness; general well being. Microbiology of sputum for effects on bacterial growth, density, antibiotic sensitivity (ID, culture, density, sensitivity of P aeruginosa, B cepacia, H influenzae and S aureus). Pulmonary function ;FEV1, FVC, forced mid-expiratory flow (FEF25-75), arterial oxygen saturation (SaO2). Response to the CF Questionnaire; Exercise performance.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female ≥ 18 years;
    2. Non-smoker;
    3. Written informed consent obtained prior to any trial specific procedures;
    4. Confirmed diagnosis of CF lung disease (i.e., respiratory clinical symptoms and positive sweat test or disease inducing mutations) by CF expert / Investigator;
    5. FEV1 40 - 80% of predicted value for age, sex and height; during 6 months prior to Screening;
    6. FEV1 within 10% of best value during 6 months prior to Screening);
    7. Regular mucus production due to CF;
    8. Ease of sputum expectoration (i.e., clearability) VAS score of  80 mm;
    9. Neutrophil elastase and / or IL-8 levels above detectable levels and/or upper limit of normal range for specified laboratory;
    10. Adequate contraceptive measures (the subject [and his/her partner] should use
    adequate contraceptive measures, consisting of two forms of contraception, at
    least one of which must be a barrier method);
    11. Able to comply with all the requirements of the protocol;
    12. Able to use inhaler satisfactorily.
    E.4Principal exclusion criteria
    1. Known sensitivity to any preparation of inhaled or parenteral heparin or the excipient leucine;
    2.Any contra indication to Monoparin® considered clinically relevant;
    3.Increased bleeding risk defined as any of :
    a.Evidence of clinically significant haemoptysis (i.e., bright red blood or substantial blood clot in sputum);or an increased risk of developing haemoptysis by virtue of previous clinical history of clinically significant haemoptysis
    b.Haemorrhage of any major organ 6 months prior to Baseline (Day 1);
    c.Patients with active gastrointestinal ulcer / bleeding during 6 months prior to Baseline (Day 1);
    d.History of heparin-induced thrombocytopaenia;
    e.Patients with bleeding diathesis defined by: i) aPTT > 25% above normal (26-36 seconds) and / or; ii) Platelet count < 100 x 106 cells/mL and / or; iii) Prothrombin time (PT) > 25% above the upper limit of normal (ULN) (i.e., 18.8s);
    f. Evidence of portal hypertension (e.g., hypersplenism or known Grade III/IV oesophageal varices;
    4. Clinically significant liver disease (e.g., known severe liver disease or cirrhosis, raised serum transaminases [ALT, AST] more than 2 x ULN), which in the opinion of the Investigator would impose a significant clinical risk;
    5. Clinically significant serious disease or organ system disease not currently controlled / stable on present therapy;
    6. Patients with a history of clinically or radiologically diagnosed aspergilloma;
    7.Pregnancy at Screening; or lactation;
    8. Planned hospitalisations which could interfere with trial compliance;
    9. Previous thoracic or scheduled major surgery during trial period;
    10. Any vaccination within 1 month of Screening;
    11. Previous or current regular use of proscribed medication defined as:
    a. Chronic / regular non-steroidal anti-inflammatory drug (NSAID) use (i.e., more than 3 times per week);
    b. Any regular anti coagulant therapy (e.g., warfarin, aspirin) in the 2 weeks prior to Screening;
    c. Any previous use of inhaled heparin;
    d. Use of parenteral heparin 1 month prior to Screening;
    e. Use of other investigational drugs 1 month prior to Screening;
    f. Chronic / regular corticosteroid (1 month prior to Screening) use except for:
    i)inhaled corticosteroids ≤ 1 mg/day of beclometasone dipropionate (BDP) or equivalent (e.g., 500 mg/day Seretide); Note: It is acceptable for the dose to be reduced 1 month prior to and during Screening as long as this lower dose subsequently remains stable. ii) systemic doses of ≤ 5 mg/day of oral prednisolone or equivalent; iii) limited dermatological use (a maximum of 3 times per week);
    g. Any regular inhaled tobramycin (Tobi®) or other antibiotic use for oral, inhaled or parenteral treatment to be stable for at least 1 month prior to Screening and during the course of the trial (e.g., erythromycin, clarithromycin; azithromycin; colistin). (Note: If dosing changes between Screening and Baseline (Day 1), the patient can not be entered in the trial);
    h.Modification of medication to treat respiratory disease between Screening and Baseline (Day 1): i) administration of additional medication for a respiratory infection such as antibiotics (e.g., any inhaled antibiotic such as Tobi® and colistin or any oral or parenteral antibiotic); ii) use of mucolytics (e.g., Pulmozyme®, erdosteine). Patients must be off Pulmozyme® for 1 month prior to Baseline (Day 1) and during the treatment period; iii) concomitant use of hypertonic saline treatment (Note: Patients treated with Pulmozyme® or hypertonic saline should have a 4 week Screening washout period, while patients not receiving these treatments are to have a minimum 2-week Screening period. Pulmozyme® and hypertonic saline cannot be used after Baseline [Day 1]).
    12. Unable for any other reason to satisfactorily comply with the protocol (e.g., attendance for trial visits, treatment or assessments).
    E.5 End points
    E.5.1Primary end point(s)
    Pharmacodynamic Endpoints
    The PD variables are:
    Expectorated mucus measurement parameters (i.e., rheological viscoelasticity / physicochemical measurement parameters) (in accordance with advised tests) (expectorated sputum samples must be collected after standard physiotherapy regime);
    Induced sputum markers (neutrophil elastase, interleukins [IL-6, IL-8 and IL-10]) and cell counts (i.e., neutrophils, macrophages) (induced samples collected at all centres; pre-dose and 1 hour post treatment and at selected centres; 1 hour post treatment and at 4 hours post treatment for inflammatory markers);
    EBC levels of pH and superoxide (and / or 8-isoprostane);
    Blood markers, neutrophil elastase, neutrophil elastase / AAT complex, neutrophil count, IL-6, IL-8, IL-10 and CRP levels;
    aPTT and platelet count.
    Evaluation of Efficacy Endpoints
    The efficacy variables are:
    VAS parameters, i.e., cough resolution; expectorated sputum clearability, thickness, volume, colour, viscoelasticity (stickiness); breathlessness; general well being (including feeling, energy, physical activity, appetite and sleep);
    Microbiology assays of expectorated sputum (i.e., analysis of bacterial growth, density, antibiotic sensitivity of the following organisms are included: Pseudomonas aeruginosa [mucoid and other types], Burkholderia cepacia, Haemophilus influenzae, Staphylococcus aureus;
    Pulmonary function parameters FEV1, FVC and FEF25-75, and SaO2 by finger oximetry at rest, post physiotherapy and before induced sputum;
    Response to the CFQ: responses to the questionnaire are to be measured by a six point Likert scale which are then transformed into values of between 0 and 100. Transformed scores of less than 50 represent negative scores, suggesting that the individuals may be experiencing difficulties within that particular domain;
    Response to 10-metre shuttle exercise test (Singh et al 1994; Serisier et al 2006).
    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 No
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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 Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E. trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA10
    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 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 years
    E.8.9.1In the Member State concerned months12
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial months12
    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) 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 Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception Information not present in EudraCT
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    F.3.3.3Pregnant women Information not present in EudraCT
    F.3.3.4Nursing women Information not present in EudraCT
    F.3.3.5Emergency situation Information not present in EudraCT
    F.3.3.6Subjects incapable of giving consent personally Information not present in EudraCT
    F.3.3.7Others Information not present in EudraCT
    F.4 Planned number of subjects to be included
    F.4.1In the member state16
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 64
    F.4.2.2In the whole clinical trial 64
    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 Decision2008-07-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2008-11-11
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2010-10-25
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