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    Summary
    EudraCT Number:2007-004435-30
    Sponsor's Protocol Code Number:M/273FO/23
    National Competent Authority:Czech Republic - SUKL
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2007-12-10
    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 ConcernedCzech Republic - SUKL
    A.2EudraCT number2007-004435-30
    A.3Full title of the trial
    A randomised, 4-week, placebo-controlled, double-blind, 6 arm parallel group, dose-finding clinical trial, to assess the efficacy and safety of three different doses of formoterol (6, 12 & 18µg) combined with the inhaled anticholinergic aclidinium bromide 200µg, aclidinium bromide 200µg monotherapy and formoterol 12µg monotherapy all administered once daily by inhalation via Almirall inhaler in patients with stable moderate to severe Chronic Obstructive Pulmonary Disease.
    A.4.1Sponsor's protocol code numberM/273FO/23
    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 SponsorLaboratorios Almirall, S.A
    B.1.3.4CountrySpain
    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 No
    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 nameAclidinium bromide 200 µg + Formoterol fumarate dihydrate 6 µg
    D.3.2Product code LAS34273 + Formoterol
    D.3.4Pharmaceutical form Inhalation powder
    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 INNAclidinium Bromide
    D.3.9.1CAS number 320345-99-1
    D.3.9.2Current sponsor codeLAS 34273
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNformoterol fumarate dihydrate
    D.3.9.1CAS number 183814-30-4
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6
    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 No
    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 nameAclidinium bromide 200 µg + Formoterol fumarate dihydrate 12 µg
    D.3.2Product code LAS34273 + Formoterol
    D.3.4Pharmaceutical form Inhalation powder
    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 INNAclidinium Bromide
    D.3.9.1CAS number 320345-99-1
    D.3.9.2Current sponsor codeLS34273
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNformoterol fumarate dihydrate
    D.3.9.1CAS number 183814-30-4
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number12
    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: 3
    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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAclidinium bromide 200 µg + Formoterol fumarate dihydrate 18 µg
    D.3.2Product code LAS34273 + Formoterol
    D.3.4Pharmaceutical form Inhalation powder
    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 INNAclidinium Bromide
    D.3.9.1CAS number 320345-99-1
    D.3.9.2Current sponsor codeLAS34273
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNformoterol fumarate dihydrate
    D.3.9.1CAS number 183814-30-4
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number18
    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: 4
    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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAclidinium Bromide
    D.3.2Product code LS34273
    D.3.4Pharmaceutical form Inhalation powder
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAclidinium Bromide
    D.3.9.1CAS number 320345-99-1
    D.3.9.2Current sponsor codeLAS34273
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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: 5
    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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameFormoterol fumarate dihydrate
    D.3.4Pharmaceutical form Inhalation powder
    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 INNformoterol fumarate dihydrate
    D.3.9.1CAS number 183814-30-4
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number12
    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 placeboInhalation powder
    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
    Moderate to severe Chronic Obstructive Pulmonary Disease (COPD).
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10009033
    E.1.2Term Chronic obstructive pulmonary disease
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the efficacy and safety of three combinations of aclidinium bromide 200µg with formoterol (6, 12 or 18µg) compared to placebo, monotherapy treatment formoterol 12µg and monotherapy treatment aclidinium bromide 200µg in patients with moderate to severe Chronic Obstructive Pulmonary Disease (COPD).

    To determine the optimal formoterol dose combined with aclidinium bromide to be investigated in subsequent clinical trials.
    E.2.2Secondary objectives of the trial
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Sub-study assessing extended serum glucose and potassium levels and 24-hour Holter ECG of which details are given on page 6 of the protocol.
    E.3Principal inclusion criteria
    1. Adult male or non-pregnant, non-lactating female aged between 40 and 80 years old, both inclusive. Women of childbearing potential are allowed to enter the trial ONLY if they use TWO medically approved contraceptive measures (i.e., mechanical and pharmacological).
    (A female is considered to be of childbearing potential unless she has had a hysterectomy, is at least one year post-menopause or has undergone tubal ligation. All women of childbearing potential must have a negative serum pregnancy test at the Screening Visit).

    2. Patient with a clinical diagnosis of stable moderate to severe COPD (stages II and III) according to the GOLD 2006 classification (http://www.goldcopd.com).

    3. Current, or ex-cigarette smoker with a smoking history of at least 10 pack-years.
    Pack-years are calculated by dividing the number of cigarettes smoked per day by 20 (the number of cigarettes in a pack) and multiplying this figure by the number of years a person has smoked. For example, a person who smokes 40 cigarettes a day and has smoked for 10 years would have a 20 pack-year smoking history (40 cigarettes per day¸ 20 cigarettes per pack = 2; 2 x 10 years of smoking = 20 pack-year history).
    Patients smoking other tobacco types will not be allowed, unless they meet the cigarette criterion as well.

    4. Patient whose FEV1 at the Screening Visit measured between 30-45 minutes post inhalation of 400 mg of salbutamol is 30% ≤ FEV1 <80% of the predicted normal value (i.e., 100 x Post-salbutamol FEV1/ Predicted FEV1 <80% and ≥ 30%).
    (Predicted normal values to be used for calculation purposes are to be based on European Community for Steel and Coal predicted values (Quanjer et al. 1993)).

    5. Patient whose FEV1/FVC at the Screening Visit measured between 30-45 minutes post inhalation of 400 mg of salbutamol is <70% (i.e., 100 x Post-salbutamol FEV1/FVC <70%).

    6. Patient whose COPD symptoms and FEV1 values at the time of randomisation are stable compared to the Screening Visit, according to the investigator’s medical judgment.

    7. Patient who is eligible and able to participate in the trial and who consent to do so in writing after the purpose and nature of the investigation have been explained.
    E.4Principal exclusion criteria
    Patients allowed to enter the trial must not present any of the following conditions at Screening Visit and/or before randomisation:

    1. History or current diagnosis of asthma, allergic rhinitis or atopy, or exercise-induced bronchospasm.

    2. Eosinophil count ≥ 600 cells/mm3.

    3. Clinically significant respiratory conditions at the time of Screening Visit defined as:
    · Use of long-term oxygen therapy > 15h/day,
    · Known active tuberculosis,
    · History of interstitial lung or pulmonary thromboembolic disease,
    · Pulmonary resection during the past 12 months,
    · History of life-threatening COPD,
    · History of bronchiectasis secondary to respiratory diseases others than COPD (e.g., cystic fibrosis, Kartagener’s syndrome, etc),
    · Patients who in the investigator’s opinion may need to stop or start pulmonary rehabilitation or undergo a thoracotomy during the trial.

    4. Hospitalisation due to COPD exacerbation, up to the 3 months prior to the Screening Visit.

    5. Signs of a COPD exacerbation or respiratory infection (including the upper respiratory tract), up to the 6 weeks prior to the Screening Visit.

    6. Clinically significant cardiovascular conditions at the time of Screening Visit defined as:
    · Myocardial infarction within the previous 6 months,
    · Unstable arrhythmia which has required changes in the pharmacological therapy or other intervention within the previous 12 months, or newly diagnosed arrhythmia within the previous 3 months.
    · Hospitalisation within the previous 12 months for heart failure functional classes III (marked limitation of activity and only comfortable at rest) and IV (need of complete rest, confinement to bed or chair, discomfort at any physical activity and presence of symptoms at rest) as per the New York Heart Association classification (www.americanheart.org)
    · Thoracic surgery within the previous 24 months

    7. Presence of symptomatic prostatic hypertrophy and/or bladder neck obstruction. (However, patients with a diagnosis of these conditions but without symptoms due to stable concomitant medication for its treatment are allowed to enter trial).

    8. Presence of narrow-angle glaucoma.

    9. History of untoward reactions or known hypersensitivity to inhaled anticholinergics (including aclidinium bromide), β2 adrenergic agonists or inhaled medication or any component thereof (including report of paradoxical bronchospasm).

    10. Life expectancy of less than 1 year.

    11. Prolonged QTcB interval (> 470 msec) in any of the ECGs performed before randomisation, and/or the use of drugs which may induce its prolongation.

    12. Clinically relevant abnormalities in laboratory results, ECG parameters (other than QTcB), or physical examination if the abnormality defines a disease state listed as an exclusion criterion, except for those related to COPD.

    13. Clinically significant diseases other than COPD, which, in the opinion of the investigator, may put the patient at risk because of the participation in the trial; or diseases which may influence the results of the study or the patient’s ability to take part in it.

    14. Patient who does not maintain regular day/night, waking/sleeping cycles (e.g., night shift workers will be excluded).

    15. Patient who intends to use any concomitant medication not permitted by this protocol or who have not undergone the required washout period for a particular prohibited medication.

    16. Patient who is unable or unlikely to be cooperative with the study requirements of taking the medication, completion of the Patient Diary and attending the clinic for study visits.

    17. Patient who is unable to properly use a dry powder or pMDI inhaler device and/or to perform acceptable and reproducible spirometry measurements as per the ATS/ERS standards (Standardisation of lung function test, 2005 18).

    18. History of drug and/or alcohol abuse or addiction during the previous 2 years.

    19. Previous participation in another clinical trial with any investigational medicinal product 6 weeks prior to the Screening Visit.
    (Patients having participated in a previous clinical trial with aclidinium bromide (Almirall product code LAS34273) will be allowed to participate in this study provided that the above criterion is fulfilled. This circumstance will be specifically recorded on the eCRF).
    E.5 End points
    E.5.1Primary end point(s)
    Primary Efficacy Variable:

    Change from baseline in the normalised FEV1 area under the curve over 12-hour (AUC 0-12) after 4 weeks of treatment.

    Secondary Efficacy Variables:

    · Change from baseline in the trough FEV1 after 4 weeks of treatment, where the trough FEV1 is defined as the average of the best technically acceptable FEV1 values measured at 23 and 24hours after the last IMP administration.
    · Change from baseline in the peak FEV1 after 4 weeks of treatment, where the peak FEV1 is defined as the maximum of the technically acceptable FEV1 values over the first 3 hours after the last IMP administration.
    · Change from baseline in the normalised FEV1 area under the curve over 3-hour (AUC 0-3) and over 6-hour (AUC 0-6) after 4 weeks of treatment.

    Additional Efficacy Variables:

    FEV1
    · Change from baseline in the trough FEV1 after 2 weeks of treatment.
    · Change from baseline in the peak FEV1 after 2 weeks of treatment.
    · Change from baseline in the normalised FEV1 AUC 0-3 after 2 weeks of treatment.
    · Change from baseline in the normalised FEV1 area under the curve over 24-hour (AUC 0-24) and between 12 and 24 hours (AUC 12-24) after 4 weeks of treatment.
    · Change from baseline in FEV1 at each time point after 4 weeks of treatment.
    · Time to peak FEV1 defined as the time interval between the time of last IMP administration and the time of the observed peak FEV1, after the first IMP administration and after 2 and 4 weeks of treatment.

    FVC and IC

    · Change from baseline in the normalised FVC and IC AUC 0-12, AUC 0-24 and AUC 12-24 after 4 weeks of treatment.
    · Change from baseline in the normalised FVC and IC AUC 0-3 after 2 and 4 weeks of treatment.
    · Change from baseline in the trough FVC after 2 and 4 weeks of treatment where the trough FVC is defined as the average of the best technically acceptable FVC values measured at 23 and 24 hours after the IMP administration.
    · Change from baseline in the trough IC after 2 and 4 weeks of treatment, where the trough IC is defined as the average of technically acceptable IC values measured at 23 and 24 hours after the IMP administration.
    · Change from baseline in the peak FVC and IC after 2 and 4 weeks of treatment, where the peak FVC and IC are defined as the maximum of the technically acceptable FVC and IC values over the first 3 hours after the IMP administration.

    Other efficacy variables

    · Averages of the day and night use of rescue medication over the last 2 weeks of treatment.
    · Change from baseline in the average of daily COPD symptom scores (breathlessness, cough, sputum and nighttime symptoms) over the last 2 weeks of treatment.

    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 No
    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 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) 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) 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.8.4.1Number of sites anticipated in Member State concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA39
    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 years0
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months10
    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) Information not present in EudraCT
    F.1.3Elderly (>=65 years) Information not present in EudraCT
    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 state55
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 195
    F.4.2.2In the whole clinical trial 513
    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)
    When the patient completes Visit 3 (Day 29) assessments or at early termination, the investigator will re-start the medication taken by the patient prior to study entry, or any other as deemed appropriate, and the patient will be deferred to his/her family doctor.
    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 Decision2008-01-18
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2008-04-14
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2008-11-10
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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