ot applicable

Conditions: Chronic obstructive pulmonary disease (COPD)
MedDRA version: 14.0Level: LLTClassification code 10010952Term: COPDSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2011-002665-38-DE

Lead Sponsor: Almirall S.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 110

Inclusion Criteria

1. Males and non-pregnant, non-lactating females aged = 40. Females at least 1 year post-menopausal, surgically sterile (defined as having a hysterectomy or tubal ligation), or practicing a medically approved and highly effective method of contraception. Women of childbearing potential must have a negative pregnancy test at the Screening Visit and have used it for at least 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.
2. Patients with a clinical diagnosis of stable moderate to severe COPD, according to the GOLD guidelines: (http://www.goldcopd.com) and stable airway obstruction. Post-salbutamol FEV1/FVC < 70% at Screening Visit (i.e., 100xpost-salbutamol FEV1/FVC <70%).
3. Patients whose FEV1 at Screening Visit measured between 10-15 min post inhalation of 400 µg of salbutamol is = 30% and <80% of the predicted normal value (i.e., 100xobserved 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).
4. Functional residual capacity (FRC) measured by body plethysmography at Screening Visit = 120% of predicted value.
Predicted normal values used for calculation purposes were to be based on European Respiratory Society (ERS) predicted values (Stocks et al 1995).
5. Current or former cigarette smokers 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.
6. Patients who understand the study procedures and are willing to participate in the study as indicated by signing the informed consent
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 100
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

1. History or current diagnosis of asthma.
2. Any respiratory tract infection (including the upper respiratory tract) or COPD exacerbation in the six weeks before Screening Visit. Patients who develop a respiratory tract infection or exacerbation during the run-in period will be discontinued from the trial before randomisation.
3. Patients who have been hospitalised for an acute COPD exacerbation within 3 months prior to Screening Visit.
4. Clinically significant respiratory conditions other than COPD, 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 Screening visit, Run in visit or Visit 1.
7. Patients with a Body Mass Index (BMI) = 40kg/m2.
8. 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.
9. Clinically significant cardiovascular conditions including:
• Myocardial infarction during the previous 6 months.
• Unstable angina, unstable arrhythmia that has required changes in the pharmacological therapy or other intervention (e.g. use of an automated implantable cardioverter-defibrillator) during the last 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) according to the New York Heart Association.
10. Patients with a resting systolic blood pressure (SBP)= 200 mm Hg, a resting diastolic blood pressure (DBP)= 120 mm Hg, or a resting heart rate = 105 bpm at Screening Visit or Visit 1.
11. Patients with non-controlled history of infection with human immunodeficiency virus (HIV) and/or active hepatitis.
12. QTc [calculated according to Fridericia’s formulae (QTc=QT/RR1/3)] above 470 milliseconds in the manual ECG reading performed at Screening Visit.
13. Patients with clinically relevant abnormalities in the results of the clinical laboratory tests, in ECG parameters other than QTc, or in the physical examination at the Screening Visit.
14. Patients with a history (within the previous 2 years) of drug and/or alcohol abuse that may prevent compliance with trial activities.
15. Patients with any other serious or uncontrolled physical or mental dysfunction that, as judged by the investigator, could place the patient at higher risk derived from his/her participation in the study, could confound the results of the study or is likely to prevent the patient from complying with the requirements of the study or completing the study.
16. Patients who could not perform repeatable pulmonary function testing for FEV1 according to ATS/ERS 2005 criteria, plethysmography attempts,

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 1. To evaluate the effect of aclidinium bromide 400 µg BID on exercise endurance compared with placebo in patients with moderate to severe chronic obstructive pulmonary disease.<br>2. To evaluate the effect of aclidinium bromide 400 µg BID on hyperinflation and dyspnoea at rest and during exercise compared with placebo in patients with moderate to severe COPD.<br>3. To assess the safety and tolerability of inhaled aclidinium bromide 400 µg BID in the same target population.;Secondary Objective: not applicable;Primary end point(s): • Change from baseline in Endurance time during constant work rate cycle ergometry to symptom limitation at 75% of Wmax after 3 weeks of treatment.;Timepoint(s) of evaluation of this end point: Please refer to point E.5.1

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Change from baseline in trough IC after 3 weeks of treatment.<br>• Changes from baseline in intensity of dyspnoea based on the Borg Scale at isotime during constant work rate cycle ergometry after 3 weeks of treatment.;Timepoint(s) of evaluation of this end point: Please refer to point E.5.2