Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   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 on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2005-005616-25
    Sponsor's Protocol Code Number:205.342
    National Competent Authority:Greece - EOF
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2006-11-16
    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 ConcernedGreece - EOF
    A.2EudraCT number2005-005616-25
    A.3Full title of the trial
    A 16-week randomised, placebo-controlled, double-blind, double-dummy, parallel-group study comparing the efficacy and safety of tiotropium inhalation solution delivered by the Respimat® inhaler (2 puffs of 2.5 µg once daily) with that of salmeterol from the hydrofluoroalkane metered dose inhaler (2 puffs of 25 µg twice daily) in moderate persistent asthma patients homozygous for B16-Arg/Arg.
    A.3.2Name or abbreviated title of the trial where available
    Tiotropium Salmeterol Study
    A.4.1Sponsor's protocol code number205.342
    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 SponsorBoehringer Ingelheim Ellas A.E
    B.1.3.4CountryGreece
    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.2.5The 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.3.1Product nameTiotropium, 5 microgram, solution for inhalation
    D.3.4Pharmaceutical form Inhalation vapour, solution
    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.3.8INN - Proposed INNTiotropium bromide
    D.3.9.2Current sponsor codeBa 679 BR
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2,5 as bromide to per actuation
    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 RoleComparator
    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.2.5The 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.3.1Product nameSerevent Evohaler
    D.3.4Pharmaceutical form Pressurised inhalation, suspension
    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.3.8INN - Proposed INNsalmeterol
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25 µg to per metered dose
    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 placeboInhalation vapour, solution
    D.8.4Route of administration of the placeboInhalation use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboPressurised inhalation, solution
    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
    Patients with moderate persistent bronchial asthma and homozygous for arginine at the 16th position of the beta-2-adrenergic receptor
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.0
    E.1.2Level LLT
    E.1.2Classification code 10003555
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Primary objective of this study is to show non-inferiority of tiotropium versus salmeterol in morning peak expiratory flow after 16 weeks of treatment. Superiority of tiotropium versus placebo should also be demonstrated
    E.2.2Secondary objectives of the trial
    To investigate efficacy and safety of tiotropium compared to salmeterol using the following secondary endpoints:
    Daily morning and evening peak expiratory flow, peak expiratory flow variability and forced expiratory volume in one second (FEV1),
    Daily questionnaire on asthma control,
    Morning pre-dose FEV1 and morning pre-dose FVC on study visits,
    Mini-Asthma Quality of Life Questionnaire on study visits,
    Vital signs and adverse events,
    Physical examination and 12-lead ECG at study end compared to the beginning of the study
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    1. Patients must be homozygous for arginine at the 16th amino acid position of the β2 adrenergic receptor (B16 Arg/Arg)
    2. All patients must sign and date an Informed Consent form for the study consistent with ICH-GCP guidelines and local legislation prior to any study related procedures which includes medication washout and restrictions
    3. Male or female outpatients between 18 and 60 years
    4. Patients must have a documented history of asthma and must be current non-smokers or ex-smokers with no more than 10 pack years
    5. All patients must be on a maintenance treatment with inhaled corticosteroids with a total daily dose of 400 - 1000 mcg budesonide or equivalent within the last 3 months and with a stable dose within the last 3 weeks
    6. Two groups of patients are eligible for this study depending on their LABA pre-treatment:
    • Patients who are on a maintenance treatment with LABAs with a total daily dose of at least 100 μg salmeterol or at least 18 μg formoterol within the last 3 months and a stable dose within the last 3 weeks are eligible if they meet the following spirometric criterion:
    Pre-bronchodilator FEV1 <=90% of predicted normal
    • Patients who have not been treated with LABAs within the last year before visit 1 are eligible if they meet the following spirometric criterion:
    Pre-bronchodilator FEV1 <=80% of predicted normal at visit 1
    7. Patients must demonstrate an increase in FEV1 of at least 12% and 200mL 45 minutes after 80 mcg ipratropium bromide administration or 30 minutes after subsequently administered 400mcg salbutamol
    E.4Principal exclusion criteria
    1. Patients with a significant disease other than asthma; a significant disease is defined as a disease which, in the opinion of the investigator, may (i) put the patient at risk because of participation in the study, (ii) influence the results of the study, or (iii) cause concern regarding the patient’s ability to participate in the study.
    2. Patients with a recent history (i.e., six months or less) of myocardial infarction
    3. Patients who have been hospitalized for heart failure (NYHA class III or IV) within the past year
    4. Patients with any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia requiring intervention or a change in drug therapy within the past year
    5. Patients with malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years. Patients with treated basal cell carcinoma are allowed.
    6. Patients with a diagnosis of chronic obstructive pulmonary disease (COPD)
    7. Patients with a history of life threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis
    8. Patients with known active tuberculosis
    9. Patients who have undergone thoracotomy with pulmonary resection. Patients with a history of thoracotomy for other reasons should be evaluated as per exclusion criterion No. 1.
    10. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to visit 1 or patients who are currently in a pulmonary rehabilitation program that will not be maintained throughout the duration of the study.
    11. Patients who are being treated with beta-blocker medication. Cardio-selective beta-blocker eye medication for treatment of non-narrow angle glaucoma are allowed.
    12. Patients who have been treated with the long-acting anticholinergic tiotropium (Spiriva®) within 4 weeks prior to visit 1
    13. Patients who were treated with cromolyn sodium or nedocromil sodium within 2 weeks prior to visit 1
    14. Patients who were treated with oral betamimetics within 2 weeks prior to visit 1
    15. Patients who were treated with oral corticosteroids within 4 weeks prior to visit 1
    16. Patients who were treated with theophylline within 2 weeks prior to visit 1
    17. Patients who were treated with leucotriene modifiers within 4 weeks prior to visit 1
    18. Patients who were treated with omalizumab within 4 weeks prior to visit 1
    19. Patients with known hypersensitivity to anticholinergic drugs or any other components of the inhalation solution used in the Respimat® inhaler
    20. Patients with known hypersensitivity to salmeterol xinafoate or any other components of the salmeterol MDI
    21. Pre-menopausal women (last menstruation ≤ 1 year prior to informed consent) who are not surgically sterile; or are nursing or pregnant; or are of child-bearing potential and are not practicing acceptable means of birth control, do not plan to continue using this method throughout the trial and do not agree to submit to periodic pregnancy testing during participation in the trial. Acceptable means of birth control include the transdermal patch, oral, implantable or injectable contraceptives, Intra Uterine Devices (IUDs), condoms, sexual abstinence and vasectomised partner. No exceptions will be made.
    22. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to visit 1
    23. Patients with previous participation (receipt of randomised treatment) in this study
    24. Patients who are currently participating in another study
    25. Patients with significant alcohol or drug abuse within the past two years
    26. Patients with any respiratory tract infection or exacerbation in the four weeks prior to visit 1 or during the run-in period. In the case of a respiratory tract infection or exacerbation of asthma during the run in period the latter may be extended by up to eight weeks. Patients may be randomised four weeks following recovery from the infection or exacerbation and three weeks after the last oral steroid and/or theophylline dose or increased dose of inhaled steroids has been given.
    27. Patients requiring more than 12 puffs of rescue medication (salbutamol MDI) per 24 hours on 3 consecutive days during the run-in period should not be randomised
    E.5 End points
    E.5.1Primary end point(s)
    Primary endpoint of this study is the change in mean weekly morning peak expiratory flow from baseline to the last week of treatment.
    Baseline is defined as the last week prior to randomisation visit
    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 Yes
    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) 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 Yes
    E.8.1.7.1Other trial design description
    Double dummy
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    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.8.5The 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
    The study will be finished when 315 patients without major protocol violations will have completed the study with all study visits.
    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 months3
    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 months3
    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 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 2006-11-16. 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 state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 328
    F.4.2.2In the whole clinical trial 474
    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 the last study visit the trial protocol stipulates a final physical examination, pulse and blood pressure measurement, 12-lead ECG, adverse event and concomitant therapy check. Additional visits might be required if persistent and unresolved adverse events have to be followed-up.
    After the study the asthma patients will be treated according to standard medical care for asthma.
    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 Decision2007-01-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2006-11-28
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2008-10-13
    For support, Contact us.
    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.

    European Medicines Agency © 1995-Sat Apr 27 15:53:22 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA