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    Summary
    EudraCT Number:2011-001524-38
    Sponsor's Protocol Code Number:M/40464/30
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2012-01-23
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2011-001524-38
    A.3Full title of the trial
    EFFICACY AND SAFETY OF ACLIDINIUM BROMIDE/FORMOTEROL FUMARATE FIXED-DOSE COMBINATIONS COMPARED WITH INDIVIDUAL COMPONENTS AND PLACEBO WHEN ADMINISTERED TO PATIENTS WITH STABLE CHRONIC OBSTRUCTIVE PULMONARY DISEASE
    Efficacia e sicurezza di associazioni a dose fissa di aclidinio bromuro/formoterolo fumarato rispetto ai singoli componenti e al placebo, quando somministrate a pazienti affetti da broncopneumopatia cronica ostruttiva (BPCO) stabile.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    EFFICACY AND SAFETY OF ACLIDINIUM BROMIDE/FORMOTEROL FUMARATE FIXED-DOSE COMBINATIONS COMPARED WITH INDIVIDUAL COMPONENTS AND PLACEBO WHEN ADMINISTERED TO PATIENTS WITH STABLE CHRONIC OBSTRUCTIVE PULMONARY DISEASE
    Efficacia e sicurezza di associazioni a dose fissa di aclidinio bromuro/formoterolo fumarato rispetto ai singoli componenti e al placebo, quando somministrate a pazienti affetti da broncopneumopatia cronica ostruttiva (BPCO) stabile.
    A.4.1Sponsor's protocol code numberM/40464/30
    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 SponsorALMIRALL SA
    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 supportAlmirall SA
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAlmirall S.A.
    B.5.2Functional name of contact pointIgnacio Sáez
    B.5.3 Address:
    B.5.3.1Street AddressLaureano Miró 408-410,
    B.5.3.2Town/ citySant Feliu de Llobregat
    B.5.3.3Post code08980
    B.5.3.4CountrySpain
    B.5.4Telephone number+34 93 2913716
    B.5.5Fax number+34 93 2913531
    B.5.6E-mailignacio.saez@almirall.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 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.3.2Product 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.3.9.2Current sponsor codeLAS40464
    D.3.9.3Other descriptive nameAclidinium bromide and Formoterol
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number400
    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 No
    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.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.3.2Product 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.3.9.2Current sponsor codeLAS40464
    D.3.9.3Other descriptive nameAclidinium bromide and Formoterol
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number400
    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 No
    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.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.3.2Product code LAS34273
    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.3.9.1CAS number 320345-99-1
    D.3.9.2Current sponsor codeLAS34273
    D.3.9.3Other descriptive nameAclidinium Bromide
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number800
    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 No
    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.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 nameFormoterol fumarate
    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.3.9.1CAS number 183814-30-4
    D.3.9.3Other descriptive nameFormoterol fumarate
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeup to
    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 No
    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 Disorder
    pazienti affetti da broncopneumopatia cronica ostruttiva
    E.1.1.1Medical condition in easily understood language
    Chronic Obstructive Pulmonary Disorder
    pazienti affetti da broncopneumopatia cronica ostruttiva
    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 14.1
    E.1.2Level SOC
    E.1.2Classification code 10038738
    E.1.2Term Respiratory, thoracic and mediastinal disorders
    E.1.2System Organ Class 10038738 - Respiratory, thoracic and mediastinal disorders
    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 long-term bronchodilation of aclidinium/formoterol fixed dose combinations compared to individual components and placebo, when administered twice daily via inhalation to COPD patients. - To assess the benefits of aclidinium/formoterol fixed dose combinations in COPD symptoms, disease-related health status and COPD exacerbations compared to individual components and placebo, when administered twice daily via inhalation to COPD patients. - To evaluate the long-term safety and tolerability of aclidinium/formoterol fixed dose combinations compared to individual components and placebo when administered twice daily via inhalation to COPD patients.
    • Valutare la broncodilatazione a lungo termine determinata dalle associazioni a dose fissa di aclidinio/formoterolo rispetto ai singoli componenti e al placebo, quando somministrate due volte al giorno per via inalatoria a pazienti affetti da BPCO. • Valutare i benefici determinati dalle associazioni a dose fissa di aclidinio/formoterolo per quanto riguarda i sintomi di BPCO, lo stato di salute correlato alla malattia e le esacerbazioni della BPCO rispetto ai singoli componenti e al placebo, quando somministrate due volte al giorno per via inalatoria a pazienti affetti da BPCO. • Valutare la sicurezza e la tollerabilità a lungo termine determinata dalle associazioni a dose fissa di aclidinio/formoterolo rispetto ai singoli componenti e al placebo, quando somministrate due volte al giorno per via inalatoria a pazienti affetti da BPCO.
    E.2.2Secondary objectives of the trial
    N/A
    N/A
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    OTHER SUBSTUDIES:
    1)protocol 2011-04-28. Final 24-hour ECG Holter
    2)protocol 2011-04-28.12-hours spirometry assessments

    ALTRI SOTTOSTUDI:
    1)protocollo 28/04/2011 elettrocardiogramma dinamico ambulatoriale nelle 24 ore
    2)protocollo 28/04/2011 valutazioni spirometriche nelle 12 ore

    E.3Principal inclusion criteria
    1. Adult male or non-pregnant, non-lactating female aged ≥40. Women of childbearing potential are allowed to enter the trial if they show to have a negative serum XML File Identifier: /jB0JiL+FSrqQCl6chyi5vJ+xb4= Page 23/34 pregnancy test at the Screening Visit and are using, during the last two months before the Screening Visit, 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 implants, injectables, oral contraceptives combined with at least one barrier method, hormonal IUDs, sexual abstinence or vasectomy of the partner. (A female is considered to be of childbearing potential unless she has had a hysterectomy, is at least one year post-menopausal or has undergone tubal ligation). 2. 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). 3. Patient with a clinical diagnosis of stable COPD according to the GOLD Guidelines at the Screening Visit (http://www.goldcopd.org). 4. Patient whose FEV1/FVC at the Screening Visit measured between 10- 15 minutes post inhalation of 400 μg of salbutamol is < 70% (i.e., 100 x Post-salbutamol FEV1 /FVC < 70%). 5. Patient with a diagnosis of moderate to severe COPD according to the GOLD Guidelines classification (stages II and III) at the Screening Visit: FEV1 measured between 10-15 minutes post inhalation of 400 μg of salbutamol is 30% ≤ FEV1 < 80% of the predicted normal value (i.e., 100 x Post-salbutamol FEV1/ Predicted FEV1 must be < 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. 199324)). 6. Patient must be able to perform repeatable pulmonary function testing for FEV1 according to ATS/ERS 2005 criteria at Screening Visit.
    1. Pazienti adulti di entrambi i sessi, di età ≥40 anni. Le donne non devono essere in stato di gravidanza e non devono allattare al seno. Le donne fertili potranno partecipare alla sperimentazione se alla visita di screening presentano un risultato negativo del test di gravidanza sul siero e stanno usando, nel corso degli ultimi due mesi prima della visita di screening, almeno un metodo di controllo delle nascite clinicamente approvato e altamente efficace, con bassa percentuale di insuccesso (ovvero meno dell'1% all'anno) quando usato costantemente e correttamente, ad esempio contraccettivi impiantati, iniettabili, orali abbinati ad almeno un metodo a barriera,dispositivi intrauterini ormonali, astinenza sessuale o vasectomia del compagno (una donna è considerata fertile a meno che non sia stata sottoposta a isterectomia, sia in post-menopausa da almeno un anno o sia stata sottoposta a legatura delle tube).
    2. Fumatori/fumatrici o ex-fumatori/fumatrici con un consumo equivalente ad almeno 10 anni-pacchetto.
    Gli anni-pacchetto si calcolano dividendo per 20 (il numero di sigarette in un pacchetto) il numero di sigarette fumate al giorno e moltiplicando la cifra ottenuta per il numero di anni per cui una persona ha fumato. Ad esempio, una persona che fumi 40 sigarette al giorno e abbia fumato per 10 anni avrebbe un consumo pari a 20 anni-pacchetto (40 sigarette al giorno ÷ 20 sigarette al pacchetto = 2; 2 x 10 anni di fumo = 20 anni-pacchetto).
    (I pazienti che fumano altro tipo di tabacco non sono ammessi, a meno che soddisfino anche il criterio di fumo di sigarette).
    3. Pazienti con diagnosi clinica di BPCO (broncopneumopatia cronica ostruttiva) stabile alla visita di screening secondo le linee guida GOLD (http://www.goldcopd.org).
    4. Pazienti il cui Volume espiratorio massimo nel 1º secondo (FEV1, Forced expiratory volume in the 1st second)/Capacità vitale forzata (FVC, Forced Vital Capacity) alla visita di screening, misurato tra 10 e 15 minuti dopo l'inalazione di 400 μg di salbutamolo, sia &lt; 70% (ovvero 100 x FEV1/FVC post salbutamolo &lt; 70%).
    5. Pazienti con diagnosi clinica di BPCO da moderata a grave alla visita di screening secondo la classificazione delle linee guida GOLD (stadi II e III): l'FEV1 misurato tra 10 e 15 minuti dopo l'inalazione di 400 μg di salbutamolo è 30% ≤ FEV1 e &lt; 80% del valore normale previsto (ovvero 100 x FEV1/FEV1 previsto post salbutamolo deve essere &lt; 80% e ≥30%). [I valori normali previsti da utilizzare per i calcoli devono essere basati sui valori previsti dalla Comunità europea del carbone e dell'acciaio (Quanjer et al. 199324)].
    6. Alla visita di screening, i pazienti devono essere in grado di eseguire test di funzionalità polmonare ripetibili per l'FEV1 secondo i criteri della Società Toracica Americana (ATS, American Thoracic Association)/Società europea di malattie respiratorie (ERS, European Respiratory Society) del 2005.
    E.4Principal exclusion criteria
    1. History or current diagnosis of asthma. 2. Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation in the 6 weeks before Screening Visit. 3. Patient hospitalised for COPD exacerbation within 3 months prior to Screening Visit. 4. Clinically significant respiratory conditions defined as: • Known active tuberculosis. • History of interstitial lung or massive pulmonary thromboembolic disease. • Pulmonary resection or lung volume reduction surgery within 12 months prior to Screening Visit. • History of lung transplantation. • Patients who in the investigator's opinion may need thoracotomy or other lung surgery during the trial. • History of bronchiectasis secondary to respiratory diseases others than COPD (e.g., cystic fibrosis, Kartagener's syndrome, etc). • Known a1-antitrypsin deficiency. 6. Use of long-term oxygen therapy (≥ 15 hours/day). 7. Patient who does not maintain regular day/night, waking/sleeping cycles including night shift workers (e.g., history of sleep apnoea syndrome, any disease related with sleep disturbances such as restless-legs syndrome or somnambulism). 8. Clinically significant cardiovascular conditions defined as: • Myocardial infarction within the 6 months prior to Screening Visit. • Thoracic surgery within 12 months prior to Screening Visit. • Unstable angina or unstable arrhythmia meaning which has required changes in the pharmacological therapy or other intervention within 12 months prior to Screening Visit, or newly diagnosed arrhythmia within the previous 3 months prior to Screening Visit. • Hospitalisation within 12 months prior to Screening Visit 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. 10. Patient with QTc [calculated according to Bazett formulae (QTc=QT/RR1/2) > 470 msec as indicated in the centralised reading report assessed at Screening Visit. 11. Patient with clinically relevant abnormalities in the results of the clinical laboratory tests, ECG parameters (other than QTc Bazzet) or in the physical examination at the Screening Visit, if the abnormality defines a disease state listed as exclusion criteria, except for those related to COPD. 12. Patient with a history of hypersensitivity reaction to inhaled anticholinergics, sympathomimetic amines, or inhaled medication or any component thereof (including report of paradoxical bronchospasm). Patient with known narrow-angle glaucoma, symptomatic bladder neck obstruction or acute urinary retention. 13. Patient with symptomatic non-stable prostatic hypertrophy. (However, patients with wellcontrolled, stable, asymptomatic benign prostatic hypertrophy are not excluded). 20. Patient unable to properly use a dry powder (DPI) or pressured metered-dose inhaler (pMDI) inhaler device or to perform spirometry measurements.
    1. Anamnesi o diagnosi attuale di asma.
    2. Qualsiasi infezione delle vie respiratorie (comprese le vie respiratorie superiori) o esacerbazione della BPCO nelle 6 settimane precedenti alla visita di screening.
    3. Ricovero ospedaliero per esacerbazione della BPCO nei 3 mesi precedenti alla visita di screening.
    4. Condizioni respiratorie clinicamente significative, definite come:
    • Tubercolosi attiva conclamata.
    • Anamnesi di malattia polmonare interstiziale o malattia tromboembolica polmonare massiva.
    • Resezione polmonare o riduzione chirurgica del volume polmonare nei 12 mesi precedenti alla visita di screening.
    • Anamnesi di trapianto del polmone.
    • Pazienti che, secondo il parere dello sperimentatore, potrebbero necessitare di toracotomia o di altro intervento chirurgico ai polmoni durante la sperimentazione.
    • Anamnesi di bronchiectasia secondaria a malattie respiratorie diverse dalla BPCO (ad es. fibrosi cistica, sindrome di Kartagener, ecc.).
    • Deficit conclamato di a1-antitripsina.
    6. Uso di ossigenoterapia a lungo termine (≥ 15 ore/giorno).
    7. Pazienti che non mantengono un ritmo giorno/notte, sonno/veglia regolare, tra cui chi lavora in turni di notte (ad es. anamnesi di sindrome da apnea nel sonno, qualsiasi malattia correlata a disturbi del sonno, quali sindrome delle gambe senza riposo o sonnambulismo).
    8. Condizioni cardiovascolari clinicamente significative, definite come:
    • Infarto miocardico nei 6 mesi precedenti alla visita di screening.
    • Intervento chirurgico al torace nei 12 mesi precedenti alla visita di screening.
    • Angina instabile o aritmia instabile, ovvero che abbia necessitato di variazioni della terapia farmacologica o di altri interventi nei 12 mesi precedenti alla visita di screening, oppure nuova aritmia diagnosticata nei 3 mesi precedenti alla visita di screening.
    • Ricovero nei 12 mesi precedenti alla visita di screening per insufficienza cardiaca di classe funzionale III (limitazione marcata dell'attività con paziente a proprio agio solo a riposo) e IV (necessità di riposo totale, confinamento a letto o su una sedia, disagio con qualsiasi attività fisica e presenza di sintomi a riposo) secondo la classificazione della New York Heart Association.
    10. Pazienti con QTc [calcolato secondo la formula di Bazett (QTc=QT/RR1/2)] &gt; 470 msec come indicato nel referto del laboratorio centralizzato, valutato alla visita di screening.
    11. Pazienti con anomalie clinicamente rilevanti nei risultati degli esami clinici di laboratorio, nei parametri dell'ECG (diversi dal QTc calcolato con la formula di Bazett) o emerse durante l'esame obiettivo alla visita di screening, se l'anomalia definisce uno stato patologico indicato tra i criteri di esclusione, fatta eccezione per quelli correlati alla BPCO.
    12. Pazienti con anamnesi di reazione da ipersensibilità agli anticolinergici inalatori, alle amine simpaticomimetiche o a farmaci inalatori oppure a qualsiasi componente che li costituisca (inclusa segnalazione di broncospasmo paradosso). Pazienti con condizione conclamata di glaucoma ad angolo stretto, ostruzione del collo vescicale sintomatica o ritenzione urinaria acuta.
    13. Pazienti con ipertrofia prostatica sintomatica instabile (i pazienti con ipertrofia prostatica benigna ben controllata, stabile e asintomatica non sono tuttavia esclusi).
    20. Pazienti che non siano in grado di utilizzare un inalatore a polvere secca (DPI, dry powder inhaler) o un inalatore pressurizzato predosato (pMDI, pressured metered-dose inhaler) oppure di eseguire misurazioni spirometriche.
    E.5 End points
    E.5.1Primary end point(s)
    Co-primary efficacy variables (at Week 24 on treatment): - Change from baseline in morning pre-dose (through) FEV1 of each aclidinium/formoterol FDC dose compared to formoterol monotherapy 12 μg. - Change from baseline in 1-hour post-morning dose FEV1 of each aclidinium/formoterol FDC dose compared to aclidinium monotherapy 400 μg.
    • Variabili di efficacia co-primarie (dopo 24 settimane di trattamento): - Variazione dal valore basale di FEV1 (valore minimo) prima della dose mattutina, determinata da ogni dose di associazione a dose fissa di aclidinio/formoterolo rispetto a 12 μg di formoterolo in monoterapia. - Variazione dal valore basale di FEV1 1 ora dopo la dose mattutina, determinata da ogni dose di associazione a dose fissa di aclidinio/formoterolo rispetto a 400 μg di aclidinio in monoterapia.
    E.5.1.1Timepoint(s) of evaluation of this end point
    at Week 24 on treatment
    alla 24a settimana di trattamento
    E.5.2Secondary end point(s)
    Improvement of TDI focal score of each aclidinium/formoterol FDC dose compared to placebo. - Change from baseline in SGRQ total score of each aclidinium/formoterol FDC dose compared to placebo.
    • Variabili di efficacia secondarie (dopo 24 settimane di trattamento): - Miglioramento del punteggio focale TDI, determinato da ogni dose di associazione a dose fissa di aclidinio/formoterolo rispetto al placebo. - Variazione dal basale del punteggio totale SGRQ, determinata da ogni dose di associazione a dose fissa di aclidinio/formoterolo rispetto al placebo.
    E.5.2.1Timepoint(s) of evaluation of this end point
    at Week 24 on treatment
    alla 24a settimana di trattamento
    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 Yes
    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 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 Yes
    E.8.2.3.1Comparator description
    - Stesso farmaco ad altro dosaggio
    - same IMP used at different dosage
    E.8.2.4Number of treatment arms in the trial5
    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 concerned13
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA17
    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
    Croatia
    Korea, Democratic People's Republic of
    Russian Federation
    South Africa
    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
    LVLS
    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 months17
    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 months17
    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.1.1Number of subjects for this age range: 0
    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: 945
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 630
    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 state48
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 1248
    F.4.2.2In the whole clinical trial 1575
    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)
    Resume medication taken by patient prior to study entry or any other
    as deemed appropriate and patient will be deferred to his/her family
    doctor.
    Riprendere i medicinali assunti dal paziente prima dell'ingresso nello studio o qualsiasi altra terapia
    ritenuta appropriata.IL paziente verrà rinviato al suo medico di famiglia.
    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 Decision2011-09-28
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-09-20
    P. End of Trial
    P.End of Trial StatusOngoing
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