ot applicable

Conditions: Chronic obstructive pulmonary disease (COPD)
MedDRA version: 16.0Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 100000004855
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2013-000116-14-HU

Lead Sponsor: ALMIRALL, S. A., Research and Development (R&D) Centre

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 900

Inclusion Criteria

For inclusion and randomisation in the trial, patients must meet each of the following criteria at Screening Visit (Visit 1) and at Visit 2 prior to randomisation.

1. Adult male or non-pregnant, non-lactating female aged = 40. Women of childbearing potential will follow specific study requirements.

Explanatory note: 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. Women of childbearing potential are allowed to enter the trial if they show to have a negative serum pregnancy test at the Screening Visit (Visit 1) 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 intra uterine devices (IUDs), sexual abstinence or vasectomy of the partner.

2. Current or ex-cigarette smoker, with a smoking history of at least 10 pack-years.

Explanatory note: Ex-smoker definition includes those patients who quit smoking more than 6 months prior to the Screening Visit. 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). When the patient has been smoker during several periods of time separated by inactivity periods, the total pack years resulting from several periods of smoking will be added up.

Patients smoking other tobacco types will not be allowed, unless they meet the cigarette criterion as well.

3. Patients with a clinical diagnosis of COPD according to GOLD guidelines 2013, with a post bronchodilator FEV1 <80%, and FEV1/FVC < 70% at Screening Visit (Visit 1).

Explanatory note: 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. 199320). (i.e., 100xpost-salbutamol FEV1/FVC <70%).

4. Symptomatic patients with a CAT=10 at Screening and Randomisation Visit (Visit 1 and 2)
Explanatory note: CAT questionnaire cannot be repeated.

5. Patient must be able to perform repeatable pulmonary function testing for FEV1 according to ATS/ERS 2005 criteria at Screening Visit.

6. 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 545
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 355

Exclusion Criteria

For inclusion and randomisation in the trial, patients must NOT meet any of the following criteria at Screening Visit (Visit 1) and at Visit 2 prior to randomisation.

1. History or current diagnosis of asthma.

2. Patients who develop a respiratory tract infection or COPD exacerbation within 6 weeks (or 3 months if hospitalisation was required) before the Screening Visit (Visit 1) or during the run-in period.

3. Clinically significant respiratory conditions

Explanatory note: Clinically significant respiratory conditions, some examples are:

-Known active tuberculosis or pulmonary hypertension.

-History of interstitial lung disorder: Exposure related interstitial lung disease; isease associated interstitial lung disease; Interstitial lung disease of distinct or unknown cause/pathology.

-History of massive pulmonary thromboembolic disease.

-History of lung lobectomy, lung volume reduction or 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

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

5. Patient who in the investigator’s opinion may need to start a pulmonary rehabilitation program during the study and/or patients who started/finished it within 3 months prior to Screening Visit.

6. Use of long-term oxygen therapy (= 15 hours/day).

7. Patients treated on daily basis with triple therapy (LABA+LAMA+ICS) within 4 weeks prior to the Screening Visit.

8. Patient who does not maintain regular day/night, waking/sleeping cycles including night shift workers.

Explanatory note: Patients with symptomatic sleep apnoea syndrome, any disease related with sleep disturbances such as restless-legs syndrome or somnambulism are to be excluded. However the use of continuous positive airway pressure (CPAP) is not an exclusion criteria.

9. Clinically significant cardiovascular conditions.

Explanatory note: Clinically significant cardiovascular conditions, some examples are:

-Myocardial infarction within the 6 months prior to Screening Visit (Visit 1)

-Unstable angina or unstable arrhythmia meaning which has required changes in the pharmacological therapy or other intervention within 12 months prior to Screening Visit (Visit 1), or newly diagnosed arrhythmia within the previous 3 months prior to Screening Visit (Visit 1).

-Hospitalisation within 12 months prior to Screening Visit (Visit 1) 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 NYHA.

10. Patient with clinically relevant abnormalities in the results of the clinical laboratory tests, ECG parameters or in the physical examination at the Screening Visit (Visit 1)

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

12. Patient with known narrow-angle glaucoma, symptomatic bladder neck obstruction, acute urinary retention, or patients

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Secondary Objective: not applicable;Primary end point(s): Peak FEV1 at week 24;Timepoint(s) of evaluation of this end point: Please refer to point E.5.1;Main Objective: 1. To assess the long term bronchodilator efficacy of Aclidinium bromide/Formoterol fumarate, administered twice a day, compared to Salmeterol/Fluticasone propionate (SeretideTM AccuhalerTM) in symptomatic COPD patients.<br><br>2. To compare the benefits of Aclidinium bromide/Formoterol fumarate, administered twice a day, versus twice-daily regimen of SeretideTM AccuhalerTM in disease-related health status and COPD symptoms.<br><br>3. To evaluate the long term safety and tolerability of Aclidinium bromide/Formoterol fumarate, administered twice a day, compared to twice daily SeretideTM AccuhalerTM in the same target population.

Secondary Outcome Measures