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    The EU Clinical Trials Register currently displays   43854   clinical trials with a EudraCT protocol, of which   7284   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:2014-005318-50
    Sponsor's Protocol Code Number:M-40464-33
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-03-09
    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 ConcernedGermany - BfArM
    A.2EudraCT number2014-005318-50
    A.3Full title of the trial
    A MULTIPLE DOSE, RANDOMISED, DOUBLE-BLIND, PLACEBO CONTROLLED, PARALLEL CLINICAL TRIAL TO ASSESS THE EFFECT OF ACLIDINIUM BROMIDE/FORMOTEROL FUMARATE FIXED-DOSE COMBINATION ON LUNG HYPERINFLATION, EXERCISE CAPACITY AND PHYSICAL ACTIVITY IN PATIENTS WITH MODERATE TO SEVERE CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD).
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical study to assess the benefits of aclidinium bromide/formoterol fumarate (active treatment) compared with placebo (comparator) in lung volumes, exercise capacity and physical activity after 8-weeks of treatment in symptomatic patients with chronic obstructive pulmonary disease (COPD). The study is "randomised" (equal chance of receiving active treatment or comparator) and "double blind" (neither patients nor the study doctor will know the treatment).
    A.3.2Name or abbreviated title of the trial where available
    Activate
    A.4.1Sponsor's protocol code numberM-40464-33
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAstraZeneca AB; Karlebyhus, Astraallén, Södertälje SE-151 85, Sweden
    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 supportAstraZeneca AB
    B.4.2CountrySweden
    B.4.1Name of organisation providing supportMenarini Group through its affiliate Berlin Chemie AG
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca
    B.5.2Functional name of contact pointInformation Centre
    B.5.3 Address:
    B.5.3.1Street AddressNot applicable
    B.5.3.2Town/ cityNot applicable
    B.5.3.3Post codeNot applicable
    B.5.3.4CountrySweden
    B.5.6E-mailinformation.center@astrazeneca.com
    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 Duaklir Genuair
    D.2.1.1.2Name of the Marketing Authorisation holderAlmirall, S.A.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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/Formoterol Fumarate 400/12 µg fixed-dose combination
    D.3.2Product code LAS40464
    D.3.4Pharmaceutical form Inhalation powder
    D.3.4.1Specific paediatric formulation No
    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.3.9.4EV Substance CodeSUB71687
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number400
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFormoterol
    D.3.9.1CAS number 183814-30-4
    D.3.9.3Other descriptive nameFORMOTEROL FUMARATE DIHYDRATE
    D.3.9.4EV Substance CodeSUB25660
    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) No
    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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Yes
    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 No
    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
    Chronic obstructive pulmonary disease (COPD)
    E.1.1.1Medical condition in easily understood language
    COPD is a chronic lung disease that causes shortness of breath and coughing.
    A bronchodilator helps to open your airways and makes it easier to get air in and out of the lungs.
    E.1.1.2Therapeutic area Diseases [C] - Respiratory Tract Diseases [C08]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10010952
    E.1.2Term COPD
    E.1.2System Organ Class 100000004855
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the effect of aclidinium bromide/formoterol 400/12μg fixed dose combination (FDC) BID on lung hyperinflation compared with placebo in patients with moderate to severe chronic obstructive pulmonary disease.
    E.2.2Secondary objectives of the trial
    To evaluate the effect of aclidinium bromide/formoterol 400/12μg fixed dose combination (FDC) BID on exercise capacity and physical activity before and after behavioural intervention compared with placebo in patients with moderate to severe chronic obstructive pulmonary disease.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Males and non-pregnant, non-lactating females aged ≥ 40.
    Explanatory note: A female is considered to be of childbearing potential unless is at least one year post-menopausal or permanently sterilised (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy). Women of childbearing potential are allowed to enter the trial if they show to have a negative pregnancy test at the Screening Visit and are using, during the last two months before the Screening Visit and during the whole duration of the trial, at least one medically approved and highly effective method of birth control defined as those which result in a low failure rate (i.e less than 1% per year) when used consistently and correctly such as oral, injected or implanted hormonal methods of contraception combined with at least one barrier method (condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository), placement of an intrauterine devices (IUDs) or intrauterine system (IUS), sexual true abstinence (when it is in line with the preferred and usual lifestyle of the subject; periodic abstinence and withdrawal are not acceptable methods) or vasectomy of the partner (when the vasectomised male partner is the sole partner). Male
    participants are not requested to use contraception methods during thier participation on the trial

    2. Patients with a clinical diagnosis of COPD according to GOLD guidelines 2014, with a post bronchodilator FEV1 ≥ 40% and < 80% of the predicted value and FEV1/FVC < 70% at Visit 1.
    Explanatory note: for the bronchodilator test administer 4 puffs of inhaled salbutamol (100 μg/puff) through a spacer device (to ensure proper inhalation) and perform 3 technically adequate spirometry between 10 to 15 minutes after inhalation. Predicted normal values based on European Community for Steel and Coal predicted values.

    3. Functional residual capacity (FRC) measured by body plethysmography at Visit 1 ≥ 120% of predicted value.
    Explanatory note: Predicted normal values used for calculation purposes were to be based on European Respiratory Society (ERS) predicted values.

    4. Patients with modified Medical Research Council dyspnea scale (mMRC) ≥ 2 at Visit 1.

    5. Current or former cigarette smokers with a smoking history of at least 10 pack-years at Visit 1
    Explanatory notes:
    - Former smoker condition defined as having quit smoking ≥ 6 months before Visit 1.
    - Pack-years is 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). In case of intermittent smoking/non-smoking periods, pack-years is calculated by summing all periods pack-years.
    - Patients smoking other tobacco types will not be allowed, unless they meet the cigarette criterion as well.

    6. Patients willing to participate in the telecoaching program during the four last weeks and to enhance their physical activity

    7. Patients who understand and are able to follow the study procedures, are cooperative and are willing to participate in the study as indicated by signing the informed consent.
    E.4Principal exclusion criteria
    1. History or current diagnosis of asthma.

    2. Any respiratory tract infection (including upper respiratory tract) or COPD exacerbation in the 6 weeks prior to Visit 1 or during the run-in period.

    3. Patients who have been hospitalised for an acute COPD exacerbation within 3 months prior to Visit 1 or during the run-in period.

    4. Clinically significant respiratory conditions other than COPD.
    Explanatory note: including
    - Known active tuberculosis.
    - History of interstitial lung or pulmonary thromboembolic disease.
    - Pulmonary resection or lung volume reduction surgery within 12 months prior to Screening Visit.
    - History of bronchiectasis secondary to respiratory diseases others than COPD (e.g., cystic fibrosis, Kartagener’s syndrome, etc).
    - History of lung transplantation.
    - Patients who in the investigator’s opinion may need pulmonary rehabilitation or thoracotomy or other lung surgery during the trial.
    - Patients with a history of a1-antitrypsin deficiency.

    5. Use of long-term oxygen therapy (≥ 15 hours/day).

    6. Oxygen saturation ≤ 85% as measured by pulse oximetry during exercise testing at Visit 1, Visit 2 or Visit 3 prior to randomisation.

    7. Patients with a Body Mass Index (BMI) ≥ 40kg/m2.

    8. Patient who may need to start a pulmonary rehabilitation program during the study and/or who started/finished it within 3 months prior to Visit 1 or during the run-in period.

    9. Patients with clinically significant cardiovascular conditions.

    10. Patients with Type I or uncontrolled Type II diabetes, uncontrolled hypo-or hyperthyroidism, hypokalaemia, or hyperadrenergic state, uncontrolled or untreated hypertension.

    11. Patient with known non-controlled history of infection with human immunodeficiency virus (HIV) and/or active hepatitis.
    Explanatory note: active hepatitis is defined as clinical symptoms associated with chronic portal inflammation with regional necrosis and fibrosis, which may progress to nodular postnecrotic cirrhosis or patients with antibody to hepatitis B core antigen (anti-HBc) and hepatitis B surface antige(HBsAg) test with positive results or anti-HCV antibody and HCV RIBAHCV positive tests or genetic material (RNA) testing positive results

    12. Patients with clinically relevant abnormalities in the results of the blood pressure, ECG, or physical examination at Visit 1.

    13. Patients with any serious or uncontrolled physical or mental dysfunction that could place the patient at higher risk derived from his/her participation in the study or could confound the results.

    14. Patients with conditions other than COPD that may contribute to dyspnoea and exercise limitation or with contraindications to clinical exercise testing according to ATS recommendations for CPET
    Explanatory note: e.g, syncope, thrombosis of lower extremities, pulmonary edema)

    15. Patients with other relevant comorbidities that make the patient nor suitable to follow-up study procedures and/or could affect physical activity

    16. Patients who cycled < 2 minutes or > 15 minutes during the constant work-rate exercise tests conducted at Visit 2 (Run-in Visit) or at Visit 3 even after adjustment of the work load.

    17. Patients with history of hypersensitivity reaction to inhaled anticholinergics, sympathomimetic amines or inhaled medication or any component thereof (including report of paradoxical bronchospasm)

    18. Patients for whom the use of anticholinergic drugs is contraindicated (acute urinary retention, symptomatic prostatic hypertrophy, bladder neck obstruction or narrow-angle glaucoma).

    19. Patients unable to properly use a multidose dry powder inhaler or a pressurized metered-dose inhaler (pMDI).

    20. Patients using any prohibited medication (including IMP within 30 days (or 6 half-lives, whichever is longer) before Visit 1) or who have not undergone the required washout period.

    21. History of malignancy of any organ system (including lung cancer), treated or untreated, within the past 5 years other than basal or squamous cell skin cancer).

    22. Patients who do not maintain regular day/night, waking/sleeping cycles (e.g., night shift workers, sleep apnea).

    23. Patients unable to give their consent, or patients of consenting age but under guardianship, or vulnerable patients
    E.5 End points
    E.5.1Primary end point(s)
    Primary Efficacy variable:

    - Change from baseline in trough Functional Residual capacity (FRC) after 4 weeks of treatment
    E.5.1.1Timepoint(s) of evaluation of this end point
    After 4 weeks of treatment
    E.5.2Secondary end point(s)
    Secondary Efficacy variable:

    - Change from baseline in Endurance Time (ET) during constant work rate cycle ergometry to symptom limitation at 75% of Wmax after 8 weeks of treatment.

    - Percentage of inactive patients (<6,000 steps per day) after 8 weeks on treatment
    E.5.2.1Timepoint(s) of evaluation of this end point
    After 8 weeks on 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 Yes
    E.6.4Safety No
    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) No
    E.7.4Therapeutic use (Phase IV) Yes
    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.8.2.4Number of treatment arms in the trial2
    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 concerned16
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA27
    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 No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    Germany
    Hungary
    Italy
    Spain
    E.8.7Trial has a data monitoring committee No
    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
    LVLS
    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 months11
    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 months11
    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 No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 160
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 108
    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 state150
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 245
    F.4.2.2In the whole clinical trial 268
    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)
    After last study procedure is performed at Visit 5, subjects should continue to take their usual medication, also allowed during the trial, and may resume other medications discontinued prior to trial enrolment (with investigator’s agreement).
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-03-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-04-07
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-07-25
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